bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyanodeoxy‐Glycosyl Derivatives as Substrates for Enzymatic Reactions
Authors: Carmona Ana T. , Fialová Pavla , Křen Vladimir , Ettrich Rudiger , Martínková Ludmila , Moreno‐Vargas Antonio J. , González Cristina , Robina Inmaculada
Published: February 2006

Synthetic routes for the preparation of new sugar nitriles 8–10 derived from 2‐acetamido‐2‐deoxy‐β‐D‐glucopyranosides bearing a cyano group at the C‐5 or C‐6 position are presented. In an attempt to prepare the glycosyl azide 10 by treatment of tosylate 23 with KCN/DMF at 60 °C, an intramolecular 1,3‐dipolar cycloaddition reaction occurred to give the highly constrained nonisolable tetrazole 24, which was readily converted into the imino‐azido compound 25 through an azido‐tetrazole tautomerism. Compounds 8 and 10 werefound to be poorer substrates of fungal β‐N‐acetylhexosaminidases than compound 9 and none of these compounds was accepted as substrates of the nitrilase or nitrile hydratase. Docking of the nitriles 8–10 in the active site of the β‐N‐acetylhexosaminidase from Aspergillus oryzae gave interaction energies comparable with the natural substrate. Based on these data, which indicate strong binding of these compounds (8 > 9 > 10) to the active site, it has been proposed that some cyano derivatives may act as competitive inhibitors of β‐N‐acetylhexosaminidases. This hypothesis is consistent with enzyme inhibition experiments which showed strong inhibitory properties of compound 9 (KI = 0.37 mM) and in particular of compound 8 (KI = 7.6 μM). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Nitrogen Functionalities in Palladium‐Catalyzed Reactions on Solid Supports: A Case Study
Authors: Knepper Kerstin , Vanderheiden Sylvia , Bräse Stefan
Published: February 2006

Three different Palladium‐catalyzed reactions (Heck, Suzuki, Sonogashira) were carried out on three different types of linkers on solid supports. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
syn‐ and anti‐Isomers of a O‐Methyloxime‐Substituted Tricyclic Ozonide
Authors: Griesbaum Karl , Frank Achim , McCullough Kevin J.
Published: February 2006

The ozonolysis of bicyclo[9.4.0]pentadec‐1(11)‐en‐12‐one (4) in pentane, followed by the treatment of the ozonolysisproduct with O‐methylhydroxylamine afforded the stable ozonides anti‐(8) and syn‐2‐O‐methyloxime‐16,17,18‐trioxatricyclo[10.3.2.1]octadecane (9). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Crucial Role of the Conjugate Base for Silyl Lewis Acid Induced Mukaiyama Aldol Reactions
Authors: Hiraiwa Yukihiro , Ishihara Kazuaki , Yamamoto Hisashi
Published: February 2006

The silyl Lewis acid induced Mukaiyama aldol reaction proceeds through each catalytic cycle under the influence of their conjugate bases; there is an especially significant difference between the low nucleophilic conjugate bases, –NTf2 and –CTf3, and the relatively high nucleophilic –OTf. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Lewis Acid Catalyzed Conjugate Addition and the Formation of Heterocycles using Michael Acceptors under Solvent‐Free Conditions
Authors: Mekonnen Alemayehu , Carlson Rolf
Published: February 2006

Conjugate addition and conjugate‐addition‐initiated ring closure (CAIRC) reactions of β‐dicarbonyl compounds with Michael acceptors have been studied using several Lewis acid catalysts under solvent‐free conditions. Excellent chemoselectivity was obtained when various Michael acceptors were treated with several β‐dicarbonyl compounds. On the other hand, 2‐bromo‐2‐cyclopentenone and 3‐bromo‐3‐vinyl methyl ketone furnished 2,3‐dihydrofurans instead of the 1,4‐adducts when treated with the same reagents.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Strategies for the Formation of Tetrahydropyran Rings in the Synthesis of Natural Products
Authors: Clarke Paul A. , Santos Soraia
Published: February 2006

This microreview surveys the literature over the last five years with regard to construction of functionalised tetrahydropyran (THP) rings in the context of the synthesis of natural products. The overview given is intended to provide a working knowledge of the area for those who are unfamiliar, and to refresh and remind those who do work in the area of the exciting developments in the field. While the construction of the THP rings in a number of natural products has been reviewed, we have attempted to highlight the different strategies by focusing on two natural products, namely phorboxazole and centrolobine as case studies. Over the last five years, these natural products have become a test bed for new methods for the construction of THP rings. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Synthesis of An Enantioenriched C2‐Symmetric Molecule by a Chiral‐Base‐Mediated Kinetic Resolution of an (Arene)tricarbonylchromium(0) Complex
Authors: Castaldi M. Paola , Gibson Susan E. , White Andrew J. P.
Published: February 2006

Trimethylsilyl substituents have been used to control the conformational preferences of a 1,2‐disubstituted (arene)tricarbonylchromium(0) complex. The kinetic resolution of the mono‐methyl derivative (±)‐11 using a chiral base/iodomethane quench sequence led to the synthesis of the enantioenriched C2‐symmetric bis‐ether (+)‐13. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Highlighting the role of the chlorine substituents in the glycopeptide antibiotic balhimycin for chiral recognition in capillary electrophoresis
Authors: Jiang Zhengjin , Bertazzo Marcelo , Süssmuth Roderich D. , Yang Zhuohong , Smith Norman Williams , Schurig Volker
Published: February 2006

The vancomycin‐type glycopeptide antibiotic balhimycin (I) and its dehaloanalogue dechlorobalhimycin (III), which is characterized by the total substitution of the two chlorine atoms of I by hydrogen, were employed as chiral selectors for the enantioresolution of 11 racemic dansyl amino acids and six 2‐arylpropionic acid nonsteroidal anti‐inflammatory racemic drugs by CE. The observed enantioresolution capability of I for all test analytes is clearly higher than that observed for III. This result suggests that chlorine substituents of I played a major role in the enantioresolution of these test analytes. A dimerization‐based mechanism is proposed in order to explain this phenomenon. The two chlorine substituents of each monomer, which mutually penetrate into the cavity of the adjacent molecule of the dimer, are assumed to promote dimerization and as a consequence also enantioresolution.
Less common applications of monoliths: I. Microscale protein mapping with proteolytic enzymes immobilized on monolithic supports
Authors: Svec Frantisek
Published: February 2006

This review summarizes the recent contributions to the rapidly growing area of immobilized enzymes employing both silica and synthetic polymer‐based monoliths as supports. Focus is mainly on immobilized proteolytic enzyme reactors designed for studies in proteomics. Porous monoliths emerged first as a new class of stationary phases for HPLC in the early 1990s. Soon thereafter, they were also used as supports for immobilization of proteins and preparation of both stationary phases for bioaffinity chromatography and enzymatic reactors. Organic polymer‐based monoliths are typically prepared using a simple molding process carried out within the confines of a “mold” such as chromatographic column or capillary. Polymerization of a mixture comprising monomers, initiator, and porogenic solvent affords macroporous materials. In contrast, silica‐based monoliths are first formed as a rigid rod from tetraalkoxysilane in the presence of PEG and subsequently encased with a plastic tube. Both types of monolith feature large through‐pores that enable a rapid flow‐through. Since all the solutions must flow through the monolith, the convection considerably accelerates mass transfer within the monolith. As a result, reactors including enzyme immobilized on monolithic support exhibit much higher activity compared to the reactions in solution.
Spatial modelling using a new class of nonstationary covariance functions
Authors: Paciorek Christopher J. , Schervish Mark J.
Published: February 2006

We introduce a new class of nonstationary covariance functions for spatial modelling. Nonstationary covariance functions allow the model to adapt to spatial surfaces whose variability changes with location. The class includes a nonstationary version of the Matérn stationary covariance, in which the differentiability of the spatial surface is controlled by a parameter, freeing one from fixing the differentiability in advance. The class allows one to knit together local covariance parameters into a valid global nonstationary covariance, regardless of how the local covariance structure is estimated. We employ this new nonstationary covariance in a fully Bayesian model in which the unknown spatial process has a Gaussian process (GP) prior distribution with a nonstationary covariance function from the class. We model the nonstationary structure in a computationally efficient way that creates nearly stationary local behaviour and for which stationarity is a special case. We also suggest non‐Bayesian approaches to nonstationary kriging.

To assess the method, we use real climate data to compare the Bayesian nonstationary GP model with a Bayesian stationary GP model, various standard spatial smoothing approaches, and nonstationary models that can adapt to function heterogeneity. The GP models outperform the competitors, but while the nonstationary GP gives qualitatively more sensible results, it shows little advantage over the stationary GP on held‐out data, illustrating the difficulty in fitting complicated spatial data. Copyright © 2006 John Wiley & Sons, Ltd.
Adaptive measurement‐based traffic engineering in small differentiated services domains
Authors: Krasser Sven , Owen Henry , Sokol Joachim , Grimminger Jochen , Huth Hans‐Peter
Published: February 2006

In this paper, we propose a framework for measurement‐based traffic engineering and connection admission control in small‐differentiated services domains. The domain investigated is a wired radio access network based on the Internet protocol (IP). This framework is evaluated by simulation using the popular network simulator ns‐2. The framework is adaptive to changes in the network load and supports multiple types of service. All traffic‐engineering decisions are made by edge routers (ERs) at the rim of the network domain. Multiple disjoint paths are configured between those ERs. Network state information is gathered in two different fashions. We evaluate a scheme based on the states of the queues on each alternative path and a scheme based on end‐to‐end probe packet transmission characteristics on each alternative path. Both schemes are compared to a shortest path first (SPF) routing approach. Copyright © 2006 AEIT
Serially concatenated continuous phase modulation with symbol interleavers: performance, properties and design principles
Authors: Xiao Ming , Aulin Tor M.
Published: February 2006

Serially concatenated continuous phase modulation (SCCPM) systems with symbol interleavers are investigated. The transmitted signals are disturbed by additive white Gaussian noise (AWGN). Compared to bit interleaved SCCPM systems, this scheme shows a substantial improvement in the convergence threshold at the price of a higher error floor. In addition to showing this property, we also investigate the underlying reason by error event analysis. In order to estimate bit error rate (BER) performance, we generalise traditional union bounds for a bit interleaver to this non‐binary interleaver. For the latter, both the order and the position of permuted non‐zero symbols have to be considered. From the analysis, some principal properties are identified. Finally, some design principles are proposed. Our paper concentrates on SCCPM, but the proposed analysis methods and conclusions can be widely used in many other systems such as serially concatenated trellis coded modulation (SCTCM) et cetera. Copyright © 2006 AEIT
Dynamic packet allocation scheme for an all‐to‐all transmission schedule in WDM networks
Authors: Wen Jyh‐Horng , Huang Kuo‐Ting , Tsai Tzu‐Chen , Yang Cheng‐Ying
Published: February 2006

In wavelength division multiplexing broadcast‐and‐select star networks, the all‐to‐all transmission schedule is suitable for the uniform traffic pattern. The system performance is seriously degraded for the non‐uniform traffic patterns. Based on the demand assignment control, a dynamic packet allocation algorithm is proposed for the all‐to‐all transmission schedule. The algorithm decomposes the traffic matrix into a transmission matrix, and a residual matrix with a simple procedure. The transmission matrix is with most entries to approach the uniform traffic matrix. Within the transmission matrix, the idle time slots could be shared with the heavy‐load input nodes to increase the packet transmission. The simulation results show that the system with applying the algorithm could efficiently promote the performance on throughput, packet delay and buffer size for non‐uniform traffic patterns. Copyright © 2006 AEIT
A fully 3D finite volume method for incompressible Navier–Stokes equations
Authors: Deponti Alberto , Pennati Vincenzo , Biase Lucia De
Published: February 2006

A semi‐implicit numerical method for the three‐dimensional incompressible Navier–Stokes equations is presented. The method describes the velocity and the non‐hydrostatic pressure field and the free surface evolution in time. The governing equations are discretized by means of the finite volume method on a structured non‐uniform grid; for this reason both local and global mass conservation are guaranteed. Convective and diffusive fluxes on the control volume faces, as well as boundary conditions, are approximated by high‐order formulae. Copyright © 2006 John Wiley & Sons, Ltd.
Hedging and value at risk
Authors: Harris Richard D. F. , Shen Jian
Published: February 2006

In this article, it is shown that although minimum‐variance hedging unambiguously reduces the standard deviation of portfolio returns, it can increase both left skewness and kurtosis; consequently the effectiveness of hedging in terms of value at risk (VaR) and conditional value at risk (CVaR) is uncertain. The reduction in daily standard deviation is compared with the reduction in 1‐day 99% VaR and CVaR for 20 cross‐hedged currency portfolios with the use of historical simulation. On average, minimum‐variance hedging reduces both VaR and CVaR by about 80% of the reduction in standard deviation. Also investigated, as an alternative to minimum‐variance hedging, are minimum‐VaR and minimum‐CVaR hedging strategies that minimize the historical‐simulation VaR and CVaR of the hedge portfolio, respectively. The in‐sample results suggest that in terms of VaR and CVaR reduction, minimum‐VaR and minimum‐CVaR hedging can potentially yield small but consistent improvements over minimum‐variance hedging. The out‐of‐sample results are more mixed, although there is a small improvement for minimum‐VaR hedging for the majority of the currencies considered. © 2006 Wiley Periodicals, Inc. Jrl Fut Mark 26:369–390, 2006
Holy mad cow! Facts or (mis)perceptions: A clinical study
Authors: Tse Yiuman , Hackard James C.
Published: February 2006

The May 20, 2003, announcement confirming diagnosis in a Canadian cow of mad cow disease caused price disturbances in livestock, grain, and stock markets. Price and time data are used to provide a clinical study on the timing, persistency, and rationality of those disturbances in different U.S. markets, showing the three types of uncertainty that C. Avery and P. Zemsky (1998) use to identify herd behavior and the resulting mispricing. Markets react at different times, showing an informational cascading pattern. Misperceptions cause futures contract and stock reactions that are unsupported by the facts. Livestock and grain futures markets reactions suggest that people would replace beef with pork. Biogenetic stocks show price disturbances for companies with no relation to screening or treatment for mad cow disease. The market reactions to the December 23, 2003, announcement of the first incidence of mad cow disease in the United States are examined to see whether the markets have learned from the May event. © 2006 Wiley Periodicals, Inc. Jrl Fut Mark 26:315–341, 2006
An empirical analysis of commodity pricing
Authors: Heaney Richard
Published: February 2006

Commodity pricing models generally explain the link between commodity prices and stock levels in terms of a stock‐out constraint or a convenience yield. Analysis of this link is provided using monthly London Metals Exchange copper, lead, and zinc prices obtained for the period November 1964 to December 2003. A Markov model, fitted to these data, supports the existence of two distinct pricing regimes while the impact of convenience yields is also identified. © 2006 Wiley Periodicals, Inc. Jrl Fut Mark 26:391–415, 2006
Nonlinear dynamics and competing behavioral interpretations: Evidence from intra‐day FTSE‐100 index and futures data
Authors: McMillan David G. , Speight Alan E. H.
Published: February 2006

Extant empirical research has reported nonlinear behavior within arbitrage relationships. In this article, the authors consider potential nonlinear dynamics within FTSE‐100 index and index‐futures. Such nonlinearity can be rationalized by the existence of transactions costs or through the interaction between informed and noise traders. They consider several empirical models designed to capture these alternative dynamics. Their empirical results provide evidence of a stationary basis term, and thus cointegration between index and index‐futures, and the presence of nonlinear dynamics within that relationship. The results further suggest that noise traders typically engage in momentum trading and are more prone to this behavior type when the underlying market is rising. Fundamental, or arbitrage, traders are characterized by heterogeneity, such that there is slow movement between regimes of behavior. In particular, fundamental traders act more quickly in response to small deviations from equilibrium, but are reluctant to act quickly in response to larger mispricings that are exposed to greater noise trader price risk. © 2006 Wiley Periodicals, Inc. Jrl Fut Mark 26:343–368, 2006
Allelotyping analysis at chromosome arm 8p of high‐grade prostatic intraepithelial neoplasia and incidental, latent, and clinical prostate cancers
Authors: Lu Wei , Takahashi Hiroyuki , Furusato Bungo , Maekawa Suguru , Ikegami Masahiro , Sudo Akemi , Egawa Shin , Hano Hiroshi
Published: February 2006

In this study, we used 7 informative microsatellite markers at 8p22, 23.1, and 23.2 in Japanese patients to compare frequency of loss of heterozygosity (LOH) in 53 lesions of high‐grade prostatic intraepithelial neoplasia (HGPIN), 38 cases (38 lesions) of incidental prostate cancer (IPC), 31 cases (41 lesions) of latent prostate cancer (LPC), and 102 cases (168 lesions) of clinical prostate cancer (CPC). The frequency of LOH at 8p22–23.2 with at least 1 marker was 0%, 33%, 57%, and 51% in the HGPIN, IPC, LPC, and CPC cases, respectively. No statistically significant difference was found at 8p22–23.2 between the types of prostate cancer. However, the frequency of 8p22 deletion was significantly higher in CPC and LPC cases than in IPC cases (P = 0.0003) or lesions (P = 0.0017). The frequency of LOH at 8p22 and 8p23.1 loci in high‐grade tumors was significantly higher than in low‐grade tumors in both the LPCs/IPCs and CPCs (P < 0.05). Allelic loss at 8p22 was significantly more frequent in CPC than in IPC (P = 0.002) and in pT4 CPC than in earlier‐stage CPC (P = 0.038). These findings suggest that deletion of 8p is an important event in both the initiation and metastasis of prostate cancer. The extremely high frequency of LOH at 8p22–23.1 in high‐grade tumors suggests the existence of a novel putative tumor‐suppressor gene associated with the progression of prostate cancer. These results should be useful in identifying the target gene of deletion at 8p. © 2006 Wiley‐Liss, Inc.
Increased seizure duration and slowed potassium kinetics in mice lacking aquaporin‐4 water channels
Authors: Binder Devin K. , Yao Xiaoming , Zador Zsolt , Sick Thomas J. , Verkman Alan S. , Manley Geoffrey T.
Published: February 2006

The glial water channel aquaporin‐4 (AQP4) has been hypothesized to modulate water and potassium fluxes associated with neuronal activity. In this study, we examined the seizure phenotype of AQP4 −/− mice using in vivo electrical stimulation and electroencephalographic (EEG) recording. AQP4 −/− mice were found to have dramatically prolonged stimulation‐evoked seizures after hippocampal stimulation compared to wild‐type controls (33 ± 2 s vs. 13 ± 2 s). In addition, AQP4 −/− mice were found to have a higher seizure threshold (167 ± 17 μA vs. 114 ± 10 μA). To assess a potential effect of AQP4 on potassium kinetics, we used in vivo recording with potassium‐sensitive microelectrodes after direct cortical stimulation. Although there was no significant difference in baseline or peak [K+]o, the rise time to peak [K+]o (t1/2, 2.3 ± 0.5 s) as well as the recovery to baseline [K+]o (t1/2, 15.6 ± 1.5 s) were slowed in AQP4 −/− mice compared to WT mice (t1/2, 0.5 ± 0.1 and 6.6 ± 0.7 s, respectively). These results implicate AQP4 in the expression and termination of seizure activity and support the hypothesis that AQP4 is coupled to potassium homeostasis in vivo. © 2006 Wiley‐Liss, Inc.
Induction of parathyroid hormone‐related peptide following peripheral nerve injury: Role as a modulator of Schwann cell phenotype
Authors: Macica Carolyn M. , Liang Guoying , Lankford Karen L. , Broadus Arthur E.
Published: February 2006

Parathyroid hormone‐related peptide (PTHrP) is widely distributed in the rat nervous system, including the peripheral nervous system, where its function is unknown. PTHrP mRNA expression has recently been shown to be significantly elevated following axotomy of sympathetic ganglia, although the role of PTHrP was not investigated. The role of PTHrP in peripheral nerve injury was investigated in this study using the sciatic nerve injury model and dorsal root ganglion (DRG) explant model of nerve regeneration. We find that PTHrP is a constitutively secreted peptide of proliferating Schwann cells and that the PTHrP receptor (PTH1R) mRNA is expressed in isolated DRG and in sciatic nerve. Using the sciatic nerve injury model, we show that PTHrP is significantly upregulated in DRG and in sciatic nerve. In addition, in situ hybridization revealed significant localization of PTHrP mRNA to Schwann cells in the injured sciatic nerve. We also find that PTHrP causes a dramatic increase in the number of Schwann cells that align with and bundle regrowing axons in explants, characteristic of immature, dedifferentiated Schwann cells. In addition to stimulating migration of Schwann cells along the axonal membrane, PTHrP also stimulates migration on a type 1 collagen matrix. Furthermore, treatment of purified Schwann cell cultures with PTHrP results in the rapid phosphorylation of the cAMP response element protein, CREB. We propose that PTHrP acts by promoting the dedifferentiation of Schwann cells, a critical requirement for successful nerve regeneration and an effect consistent with known PTHrP functions in other cellular differentiation programs. © 2006 Wiley‐Liss, Inc.
Sphingosine‐1‐phosphate is released by cerebellar astrocytes in response to bFGF and induces astrocyte proliferation through Gi‐protein‐coupled receptors
Authors: Bassi Rosaria , Anelli Viviana , Giussani Paola , Tettamanti Guido , Viani Paola , Riboni Laura
Published: February 2006

The mitogenic role of sphingosine‐1‐phosphate (S1P) and its involvement in basic fibroblast growth factor (bFGF)‐induced proliferation were examined in primary cultures of cerebellar astrocytes. Exposure to bFGF resulted in a rapid increase of extracellular S1P formation, bFGF inducing astrocytes to release S1P, but not sphingosine kinase, in the extracellular milieu. The SK inhibitor N,N‐dimethylsphingosine inhibited S1P release as well as bFGF‐induced growth stimulation. S1P application in quiescent astrocytes caused a dose‐dependent increase in DNA synthesis. This gliotrophic effect was induced by a brief exposure to low nanomolar S1P, mimicked by the S1P receptor agonist dihydro‐S1P, and inhibited by pertussis toxin (PTX), an inactivator of Gi/Go‐proteins. S1P also induced activation of extracellular signal‐regulated kinase that was inhibited again by PTX. Moreover, the S1P lyase inhibitor 4‐deoxypyridoxine induced the cellular accumulation of S1P but did not affect DNA synthesis. These results support the view that S1P exerted a mitogenic effect on cerebellar astrocytes extracellularly, most likely through cell surface S1P receptors. In agreement, mRNAs for S1P1, S1P2, and S1P3 receptors are expressed in cerebellar astrocytes (Anelli et al., 2005. J Neurochem 92:1204–1215). Ceramide, a negative regulator of astrocyte proliferation and down‐regulated by bFGF (Riboni et al., 2002. Cerebellum 1:129–135), efficiently inhibited S1P‐induced proliferation. The S1P action appears to be part of an autocrine/paracrine cascade stimulated by bFGF and, together with ceramide down‐regulation, essential for astrocytes to respond to bFGF. The results suggest that S1P and bFGF/S1P may play an important role in physiopathological glial proliferation, such as brain development, reactive gliosis and brain tumor formation. © 2006 Wiley‐Liss, Inc.
Cyclic AMP synergistically enhances neuregulin‐dependent ERK and Akt activation and cell cycle progression in Schwann cells
Authors: Monje Paula V. , Bartlett Bunge Mary , Wood Patrick M.
Published: February 2006

The elevation of intracellular cAMP synergistically enhances the neuregulin‐dependent proliferation of cultured Schwann cells (SCs); however, the mechanism by which this occurs has not been completely defined. To better understand this mechanism, we investigated the effect of cAMP on the activation of the extracellular signal‐regulated kinase (ERK) and phosphoinositide 3‐kinase (PI3‐K)‐Akt (PKB) pathways by heregulin, a member of the neuregulin family. Using primary cultures of adult SCs, we demonstrated that the adenylyl cyclase activator, forskolin, enhanced heregulin‐dependent SC proliferation by reducing the time required for S‐phase entry. When cAMP levels were increased, using either forskolin or a cell permeable analogue of cAMP, the heregulin‐induced phosphorylation of ERK was converted from transient to sustained and the heregulin‐induced phosphorylation of Akt was synergistically increased. Consistent with these observations, studies in which inhibitors of MEK, the upstream stimulating ERK kinase, and PI3‐K were administered at different times following the onset of stimulation indicated that sustained high levels of both MEK/ERK and PI3‐K/Akt activity before S‐phase initiation were essential for S‐phase entry. Overall, these novel results indicate that in neuregulin‐stimulated SCs the activation of cAMP‐mediated pathways accelerates G1‐S progression by prolonging ERK activation and concurrently enhancing Akt activation. © 2006 Wiley‐Liss, Inc.
Fish consumption and breast cancer risk. The European Prospective Investigation into Cancer and Nutrition (EPIC)
Authors: Engeset Dagrun , Alsaker Elin , Lund Eiliv , Welch Ailsa , Khaw Kay‐Tee , Clavel‐Chapelon Françoise , Thiébaut Anne , Chajès Véronique , Key Timothy J , Allen Naomi E , Amiano Pilar , Dorronsoro Miren , Tjønneland Anne , Stripp Connie , Peeters Petra HM , van Gils Carla H , Chirlaque Maria‐Dolores , Nagel Gabriele , Linseisen Jakob , Ocké Marga C , Bueno‐de‐Mesquita H Bas , Sacerdote Carlotta , Tumino Rosario , Ardanaz Eva , Sánchez Maria‐Jose , Panico Salvatore , Palli Domenico , Trichopoulou Antonia , Kalapothaki Victoria , Benetou Vicky , Quirós J Ramón , Agudo Antonio , Overvad Kim , Bjerregaard Lone , Wirfält Elisabet , Schulz Mandy , Boeing Heiner , Slimani Nadia , Riboli Elio
Published: February 2006

There is current interest in fish consumption and marine omega‐3 (n‐3) fatty acids and breast cancer risk. Some in vitro and animal studies have suggested an inhibitory effect of marine n‐3 fatty acids on breast cancer growth, but the results from epidemiological studies that have examined the association between fish consumption and breast cancer risk in humans are inconsistent. We examined fish consumption and breast cancer risk in 310,671 women aged between 25 and 70 yr at recruitment into the European Prospective Investigation Into Cancer and Nutrition (EPIC). The participants completed a dietary questionnaire between 1992–98 and were followed up for incidence of breast cancer for a median of 6.4 yr. Hazard ratio for breast cancer by intake of total and lean and fatty fish were estimated, stratified by study centre and adjusted for established breast cancer risk factors. During follow‐up, 4,776 invasive incident breast cancers were reported. No significant associations between intake of total fish and breast cancer risk were observed, hazard ratio (HR) 1.01 (95% confidence interval [CI] 0.99–1.02; p = 0.28 per 10 g fish/day). When examining lean and fatty fish separately, we found a positive significant association only in the highest quintile for fatty fish (HR 1.13, 95% CI 1.01–1.26), but test for trend was not significant (p = 0.10). No associations with breast cancer risk were observed when the study participants were subdivided by menopausal status. Although the period of follow‐up is relatively short, the results provide no evidence for an association between fish intake and breast cancer risk. © 2006 Wiley‐Liss, Inc.
Tumor selective replication of Newcastle disease virus: Association with defects of tumor cells in antiviral defence
Authors: Fiola Christoph , Peeters Ben , Fournier Philippe , Arnold Annette , Bucur Mariana , Schirrmacher Volker
Published: February 2006

To investigate tumor‐selective viral replication, we compared several tumorigenic human cell lines to nontumorigenic human cells from the blood for the sensitivity to become infected by a recombinant lentogenic strain of Newcastle Disease Virus (NDV) with incorporated transgene EGFP (NDFL‐EGFP). Although fluorescence signals in nontumorigenic cells were only weak or missing completely, a massive and long‐lasting transgene‐expression was observed in all tumor cell lines. The majority of tumor cells (50–95%) could be infected, and viral replication was associated with an increase in the cell surface density of viral antigens. To clarify the underlying mechanism of the observed difference in virus susceptibility we examined the kinetics of interferon‐induced antiviral enzymes because NDV is a strong type‐I interferon inducer. This analysis revealed several defects of tumor cells in their antiviral defence responses: They showed no response to UV‐inactivated NDV, whereas nontumorigenic cells reacted with induction of high‐levels of the antiviral enzymes PKR and MxA. Upon coincubation with live NDV, tumor cells showed a delayed response in the increased expression of the antiviral enzymes in comparison with PBMC. In nontumorigenic cells the replication cycle of NDV stopped after the production of positive‐strand RNA, while tumor cells continued in the replication cycle and copied viral genomes 10–50 hr after infection. These results can explain the tumor selective replication behavior of this interesting antineoplastic virus. © 2006 Wiley‐Liss, Inc.
Iressa induces cytostasis and augments Fas‐mediated apoptosis in acinic cell adenocarcinoma overexpressing HER2/neu
Authors: Piechocki Marie P. , Yoo George H. , Dibbley Susan K. , Amjad Esmael H. , Lonardo Fulvio
Published: February 2006

Understanding the role of signal transduction in regulating pathways responsible for cell growth, survival and apoptosis is critical for cancer therapy. We developed and characterized a HER2/neu and Fas overexpressing cell line (BNT.888 ACA2) from a salivary gland adenocarcinoma that arose in a HER2/neu transgenic mouse. We evaluated the effects of Iressa on signal transduction networks downstream of the activated HER2 and the impact on proliferation, cell cycle and apoptosis. Iressa treatment diminished phosphorylation of the HER2/neu and EGFR. Phosphorylation of STAT‐3 also decreased and mitogenic signaling through the MAPK pathways was greatly reduced. Cyclin D1 levels decreased, and cells were arrested in G0 and failed to enter S‐phase because of hypophosphorylation of Rb and to traverse the G2M checkpoint because of degradation of cyclin B1. Cytostasis occurred within 48 hr at 250–500 nM Iressa. Levels of proapoptotic factors (bim and bax) increased and levels of antiapoptotic factors (bcl‐2 and bcl‐xL) decreased in a dose‐dependent manner. Higher doses of Iressa diminished phosphorylation of Akt slightly, but failed to induce apoptosis. Fas antibody was a potent agonist of apoptosis. Pretreatment with Iressa (1 μM, 24 hr) greatly enhanced Fas‐mediated apoptosis as determined by Annexin V binding, cleavage of caspase‐3 and PARP. Augmentation of apoptosis was associated with increased Fas expression and membrane localization. Iressa pretreatment increased bid activation, cleavage of caspases ‐3, ‐9 and ‐12 and stress signaling via c Jun. These data showing that Iressa induces cytostasis and primes the extrinsic (Fas) and intrinsic (mitochondrial and endoplasmic reticulum) apoptotic pathways should lead to the development of novel therapeutic targets and strategies. © 2006 Wiley‐Liss, Inc.
A long‐term follow‐up study on the natural course of snus‐induced lesions among Swedish snus users
Authors: Roosaar Ann , Johansson Anna L.V. , Sandborgh‐Englund Gonilla , Nyrén Olof , Axéll Tony
Published: February 2006

Snus‐induced lesions (SILs) are mucosal changes that are regularly seen in users of moist snuff (snus). Their role in oral carcinogenesis remains undefined. Our aim was to assess the natural course of SILs over several decades. A cohort of 1,115 individuals with SILs, confirmed in 1973–1974 during a population‐based survey was followed for 27–29 years through multiple record linkages with virtually complete population‐ and health registers. A sample (n = 267) of the cohort members were invited for reexamination after 19–22 years. Register‐based follow‐up through January 2002 revealed a total of 3 incident cases of oral cancer (standardized incidence ratio of 2.3, 95% CI 0.5–6.7), none of which occurred at the site of the original SIL. There was a strong association noted between the degree of SIL and current snus consumption. The SILs had disappeared in all 62 individuals who had permanently quitted using snus. In no case did we observe an important clinical change for the worse among individuals who had decreased their use or continued unabatedly. While the incidence of oral cancer in this cohort of individuals with SILs tended to be higher than expected, we conclude that cancers rarely occur at the site of lesions observed in the distant past. © 2006 Wiley‐Liss, Inc.
Enhancement of myoblast microencapsulation for gene therapy
Authors: Li Anna Aihua , Shen Feng , Zhang Tao , Cirone Pasquale , Potter Murray , Chang Patricia L
Published: February 2006

One method of nonviral‐based gene therapy is to implant microencapsulated nonautologous cells genetically engineered to secrete the desired gene products. Encapsulating the cells within a biocompatible permselective hydrogel, such as alginate‐poly‐L‐lysine‐alginate (APA), protects the foreign cells from the host immune system while allowing diffusion of nutrients and the therapeutic gene products. An important consideration is which kind of cells is the best candidate for long‐term implantation. Our previous work has shown that proliferation and differentiation of encapsulated C2C12 myoblasts in vitro are significantly improved by inclusion of basic fibroblast growth factor (bFGF), insulin growth factor II (IGF‐II), and collagen within the microcapsules (“enhanced” capsules). However, the effects of such inclusions on the functional status of the microcapsules in vivo are unknown. Here we found that comparing the standard with the enhanced APA microcapsules; there was no difference in the rates of diffusion of recombinant products of different sizes, that is, human factor IX (FIX, 65 kDa), murine IgG (150 kDa), and a lysosomal enzyme, β‐glucuronidase (300 kDa), thus providing a key requirement of such an immunoprotective device. Furthermore, the creatine phosphokinase activity and myosin heavy chain staining (markers for differentiation of the myoblasts) and the cell number per capsule in the enhanced microcapsules indicated a higher degree of differentiation and proliferation when compared to the standard microcapsules, thus demonstrating an improved microenvironment for the encapsulated cells. Efficacy was tested in a melanoma cancer tumor model by treating tumor induced by B16‐F0/neu tumor cells in mice with myoblasts secreting angiostatin from either the standard or enhanced APA microcapsules. Mice treated with enhanced APA‐microcapsules had an 80% reduction in tumor volume at day 21 compared to a 70% reduction in those treated with standard APA‐microcapsules. In conclusion, enhancement of APA microcapsules with growth factors and collagen did not adversely affect their permeability property and therapeutic efficacy. However, the enhanced differentiation and viability of the encapsulated myoblasts in vivo should be advantageous for long‐term delivery with this method of gene therapy. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Composite coating of bonelike apatite particles and collagen fibers on poly L‐lactic acid formed through an accelerated biomimetic coprecipitation process
Authors: Chen Yun , Mak Arthur F. T. , Wang Min , Li Jiashen
Published: February 2006

Collagen and apatite were coprecipitated as a composite coating on poly L‐lactic acid (PLLA) in an accelerated biomimetic process. The incubation solution contained collagen (1 g/L) and simulated body fluid with 5 times inorganic ionic concentrations as human blood plasma. The coating formed on PLLA films and scaffolds after a 24‐h incubation was characterized by using energy‐dispersive X‐ray spectroscopy, X‐ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy (SEM). It was shown that the coating contained carbonated bonelike apatite and collagen, which was similar in composition to natural bone. SEM showed a complex composite coating of submicron bonelike apatite particulates combined with collagen fibrils. It is expected that such biocomposite coating may better facilitate cell interaction and osteoconductivity. This work provided an efficient process to obtain bonelike apatite/collagen composite coating, which is potentially useful in bone tissue engineering. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
PLA stereocopolymers as sources of bioresorbable stents: Preliminary investigation in rabbit
Authors: Lafont Antoine , Li Suming , Garreau Henri , Cornhill Frederic , Vert Michel
Published: February 2006

The aim of the present work was to evaluate whether the degradation of PLA‐based bioresorbable stents can be modulated via the configuration of repeating units as it is the case in other applications like osteosynthesis. The first obstacle was finding a stent design that could allow implantation in the aorta of a rabbit taken as a model of a human coronary artery. In the absence of guidelines other than those tentatively proposed in patents, several simple designs were considered that allowed us to evaluate the fate of the stents made of poly(lactic acid) stereocopolymers with L/(L + D) ratio of 0.92 (PLA92) and 0.50 (PLA50) up to 6 months post in vivo implantation. Our findings show the feasibility of bioresorbable stenting using PLA stereocopolymers and that PLA50 degraded faster than PLA92. Therefore, using stereocopolymers appears as a means to vary the degradation rate and adapt it to the artery remodelling process that is very much dependent on the release of the stenting stress protection. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
A mechanism on why slower polymerization of a dental composite produces lower contraction stress
Authors: Feng L. , Suh B. I.
Published: February 2006

It has been well documented that the rate of polymerization of a dental composite often affects its polymerization contraction stress. In most cases, a slower cure produces a lower stress. To investigate the mechanism behind this, we prepared an unfilled dimethacrylate resin sample and photocured it using two light irradiances, both with the same total irradiation energy. We measured the polymerization‐induced shrinkage from the unbonded surface of a class I restoration, contraction stress, extent of polymerization, and flexural modulus. The resin specimens cured under the two irradiances achieved the same extent of polymerization and developed an identical amount of shrinkage from the unbonded surface. But those cured under the lower irradiance possessed a lower contraction stress and a lower flexural modulus than those cured under the higher irradiance. We demonstrated that the stress level did not respond to the extent of viscous flow of the curing resin because the slower polymerization did not produce more shrinkage from the unbonded surface. Instead, the lower stress is likely due to a lower modulus of the cured resin. To explain why the cured resin with an identical extent of polymerization can have different moduli, we proposed that slower polymerization produces a higher level of structural inhomogeneity, which reduces the rigidity of the cured resin. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Oxidation and oxidation potential in contemporary packaging for polyethylene total joint replacement components
Authors: Costa Luigi , Bracco Pierangiola , Brach del Prever Elena Maria , Kurtz Steven M. , Gallinaro Paolo
Published: February 2006

The packaging and chemical stability of both conventional and highly crosslinked polyethylene (PE) components available for clinical use in Italy were analyzed. A total of 100 sterilized PE components were entered by 18 orthopedic manufacturers into the study. Six of the manufacturers were Italian and the remaining were based in Europe or America. Hydroperoxide, oxidation, and trans‐vinylene levels within the PE components were characterized using Fourier‐transform infrared spectroscopy (FTIR). None of the 31 gas‐sterilized components had detectable free radicals, hydroperoxide content, or oxidation. Among radiation‐sterilized inserts, the highest oxidation and hydroperoxide levels were associated with gas‐permeable and polymer‐barrier packaging. To the authors' knowledge, this is the first study that relates elevated oxidation and hydroperoxide content in γ‐sterilized PE components to certain types of contemporary, polymeric barrier packaging. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Cytotoxic effects of dental desensitizers on human gingival fibroblasts
Authors: Sengun A. , Buyukbas S. , Hakki S. S.
Published: February 2006

The purpose of this study was to evaluate the effects of three different desensitizers on the cell viability and morphology of human gingival fibroblasts (HGF). Human gingival tissues were obtained from individuals who have clinically, healthy periodontium. HGF were grown at 37°C in humidified atmosphere of 5% CO2 in Dulbecco's modified eagle's medium, supplemented with glutamine, penicillin, streptomycin, and 10% fetal bovine serum. The cells were treated with different concentrations (0.1, 0.3, and 0.5 μL/mL) of desensitizers (Gluma Desensitizer, Seal&Protect, and MicroPrime). After 24‐ and 48‐h exposure to the desensitizer solutions, the viable cells were examined using a hemocytometer. To monitor HGF viability, 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl tetrazolium bromide (MTT) colorimetric assay was used and cell morphology was also observed at 48 h. Following exposure to concentrations of 0.1 μL/mL of test materials for 24 h, cell survival rates for Gluma Desensitizer (106%) and Micro Prime (62%) were not significantly different from the control, while it was significant for Seal&Protect (50%). Growing cells were significantly inhibited by all tested materials for 48 h (p < 0.05) in survival rates of 51, 47, and 31%, respectively. On the basis of the MTT assay, the cytotoxic effect of MicroPrime was more prominent, especially at high concentrations, than does Gluma Desensitizer and Seal&Protect. After exposure to Seal&Protect and MicroPrime, HGF became retracted, rounded in appearance and had loss of normal organization, leading to enlargement of intercellular space when compared with Gluma Desensitizer. As a conclusion, taking the limitations of an in vitro experiment into consideration, the cytotoxic effects were varied, depending on the chemical composition and exposure periods of the tested desensitizers. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
The nature of platinum in silicones for biomedical and healthcare use
Authors: Lambert James M.
Published: February 2006

Silicone is an important biomaterial in many different biomedical and healthcare applications. Network formation in one type of silicone relies upon a chemical crosslinking reaction that typically employs a platinum catalyst. As a consequence, low concentrations of platinum may remain in certain medical devices designed for human use. The characteristics of platinum in silicone before, during, and after the crosslinking reaction have been well described in the literature. This review summarizes the relevant literature on the organometallic and analytical chemistry of platinum in silicone and thus provides a foundation for understanding the effects this platinum may have, if any, in the various biomedical and healthcare applications where it may be present. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Synthesis and performance of amphiphilic copolymers for blood cell separation
Authors: Natori Shizue Hayashi , Gomei Yumiko , Higuchi Akon
Published: February 2006

Three types of amphiphilic copolymers using n‐butylmethacrylate (BMA) as a hydrophobic monomer, and each of N,N′‐dimethylacrylamide (DMA), N‐acryloylmorpholine (AMO), and N‐vinylpyrrolidone (VP) as hydrophilic comonomers were synthesized for coating filters used to remove leukocytes. The influence of the amphiphilic property of the resulting filters, which were composed of nonwoven fabrics coated with the above copolymers, on leukocyte removal and platelet permeation through the filters from whole blood was investigated. The platelet permeation ratio through hydrophobic noncoated filters was only 0.2%, because platelets in whole blood adhered easily to the hydrophobic filter material. However, filters coated with poly(AMO‐co‐BMA) of high AMO content showed a much higher platelet permeation ratio (nearly 90%). Further, the filters coated with poly(DMA‐co‐BMA) also showed high permeation ratios of platelets (more than 78%) over a broad range of DMA content in the copolymer. On the other hand, the coated filters showed slightly a higher permeation ratio of leukocytes than did the noncoated filters, resulting from the increase in hydrophilicity of the surface of the filters. Moreover, the coating of the amphiphilic copolymers on the surface of the nonwoven fabrics may have affected the pore size of the filters, affecting the permeation ratio of leukocytes more strongly than that of platelets. The coated filters effectively improved platelet permeation through the filters, with a slight increase in the permeation ratio of leukocytes. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006