bluuebunny/crossref_metadata_2025 huggingface dataset:
Tanshinone IIA from Salvia miltiorrhiza BUNGE inhibits human aortic smooth muscle cell migration and MMP‐9 activity through AKT signaling pathway
Authors: Jin Un‐Ho , Suh Seok‐Jong , Chang Hyen Wook , Son Jong‐Keun , Lee Seung Ho , Son Kun‐Ho , Chang Young‐Chae , Kim Cheorl‐Ho
Published: November 2007

Smooth muscle cell (SMC) migration plays an important role in normal angiogenesis and is relevant to disease‐related vascular remodeling in conditions such as brain arteriovenous malformations, pulmonary hypertension, arteriosclerosis, and restenosis after angioplasty. In this present study, we showed that tanshinone IIA, the major lipid‐soluble pharmacological constituent of Salvia miltiorrhiza BUNGE, inhibits human aortic smooth muscle cell (HASMC) migration and MMP‐9 activity. Tanshinone IIA significantly inhibited IκBα phosphorylation and p65 nuclear translocation through inhibition of AKT phosphorylation. Tanshinone IIA inhibited TNF‐α‐induced ERK and c‐jun phosphorylation, but not other MAPKs such as JNK and p38. Tanshinone IIA also inhibited NF‐κB and AP‐1 DNA‐binding. Moreover, tanshinone IIA inhibited the migration of TNF‐α‐induced HASMCs. Our results provide evidence that tanshinone IIA has multiple effects in the inhibition of HASMC migration and may offer a therapeutic approach to block HASMC migration. J. Cell. Biochem. 104: 15–26, 2008. © 2007 Wiley‐Liss, Inc.
Gravitational unloading induces an anti‐angiogenic phenotype in human microvascular endothelial cells
Authors: Mariotti Massimo , Maier Jeanette A.M.
Published: November 2007

Creating conditions similar to those occurring during exposure of cells to microgravity modulates endothelial functions. We have previously demonstrated that human macrovascular endothelial cells in simulated hypogravity proliferate faster than controls, partly because they downregulate interleukin 1α. On the contrary, murine microvascular endothelial cells are growth inhibited in simulated hypogravity, and this is due, at least in part, to the decrease of interleukin 6. Since endothelial cells are very heterogeneous and differences between various species have been reported, we exposed human microvascular cells to gravitational unloading and found that it retards cell growth without affecting cell migration. Interestingly, we detected the induction of Tissue Inhibitor of Metalloprotease‐2, which inhibits endothelial growth in vitro and angiogenesis in vivo. Together with the finding that hypogravity stimulates the synthesis of nitric oxide, involved also in neovascularization, our results underscore a modulation of the angiogenic properties of microvascular human endothelial cells. We also show that hypogravity inhibits proteasome activity, thus suggesting that post‐translational mechanisms are involved in the adaptations of these cells to hypogravity. These results underscore that hypogravity differently impacts on micro‐ and macro‐vascular human endothelial cells. In particular, these results may shed some light on the molecular mechanisms contributing to the impairment of angiogenesis observed in different models in space. Our data might also explain why bioengineered tissues to be used for regenerative medicine fail to neovascularize when assembled in simulated hypogravity. J. Cell. Biochem. 104: 129–135, 2008. © 2007 Wiley‐Liss, Inc.
N‐Glycosylation affects the adhesive function of E‐Cadherin through modifying the composition of adherens junctions (AJs) in human breast carcinoma cell line MDA‐MB‐435
Authors: Zhao Hongbo , Liang Yulong , Xu Zhibin , Wang Liying , Zhou Feng , Li Zengxia , Jin Jiawei , Yang Yong , Fang Zhengyu , Hu Yali , Zhang Lineng , Su Jianmin , Zha Xiliang
Published: November 2007

E‐cadherin mediates calcium‐dependent cell–cell adhesion between epithelial cells. The ectodomain of human E‐cadherin contains four potential N‐glycosylation sites at Asn residues 554, 566, 618, and 633. In this study, the role of N‐glycosylation in E‐cadherin‐mediated cell–cell adhesion was investigated by site‐directed mutagenesis. In MDA‐MB‐435 cells, all four potential N‐glycosylation sites of human E‐cadherin were N‐glycosylated. Removal of N‐glycan at Asn‐633 dramatically affected E‐cadherin stability. In contrast, mutant E‐cadherin lacking the other three N‐glycans showed similar protein stability in comparison with wild‐type E‐cadherin. Moreover, N‐glycans at Asn‐554 and Asn‐566 were found to affect E‐cadherin‐mediated calcium‐dependent cell–cell adhesion, and removal of either of the two N‐glycans caused a significant decrease in calcium‐dependent cell–cell adhesion accompanied with elevated cell migration. Analysis of the composition of adherens junctions (AJs) revealed that removal of N‐glycans on E‐cadherin resulted in elevated tyrosine phosphorylation level of β‐catenin and reduced β‐ and α‐catenins at AJs. These findings demonstrate that N‐glycosylation may affect the adhesive function of E‐cadherin through modifying the composition of AJs. J. Cell. Biochem. 104: 162–175, 2008. © 2007 Wiley‐Liss, Inc.
Conversion of immortal liver progenitor cells into pancreatic endocrine progenitor cells by persistent expression of Pdx‐1
Authors: Jin Cai‐Xia , Li Wen‐Lin , Xu Fang , Geng Zhen H. , He Zhi‐Ying , Su Juan , Tao Xin‐Rong , Ding Xiao‐Yan , Wang Xin , Hu Yi‐Ping
Published: November 2007

The conversion of expandable liver progenitor cells into pancreatic beta cells would provide a renewable cell source for diabetes cell therapy. Previously, we reported the establishment of liver epithelial progenitor cells (LEPCs). In this work, LEPCs were modified into EGFP/Pdx‐1 LEPCs, cells with stable expression of both Pdx‐1 and EGFP. Unlike previous work, with persistent expression of Pdx‐1, EGFP/Pdx‐1 LEPCs acquired the phenotype of pancreatic endocrine progenitor cells rather than giving rise to insulin‐producing cells directly. EGFP/Pdx‐1 LEPCs proliferated vigorously and expressed the crucial transcription factors involved in beta cell development, including Ngn3, NeuroD, Nkx2.2, Nkx6.1, Pax4, Pax6, Isl1, MafA and endogenous Pdx‐1, but did not secrete insulin. When cultured in high glucose/low serum medium supplemented with cytokines, EGFP/Pdx‐1 LEPCs stopped proliferating and gave rise to functional beta cells without any evidence of exocrine or other islet cell lineage differentiation. When transplanted into diabetic SCID mice, EGFP/Pdx‐1 LEPCs ameliorated hyperglycemia by secreting insulin in a glucose regulated manner. Considering the limited availability of beta cells, we propose that our experiments will provide a framework for utilizing the immortal liver progenitor cells as a renewable cell source for the generation of functional pancreatic beta cells. J. Cell. Biochem. 104: 224–236, 2008. © 2007 Wiley‐Liss, Inc.
Internal energy distribution of peptides in electrospray ionization : ESI and collision‐induced dissociation spectra calculation
Authors: Pak Alireza , Lesage Denis , Gimbert Yves , Vékey Károly , Tabet Jean‐Claude
Published: November 2007

The internal energy of ions and the timescale play fundamental roles in mass spectrometry. The main objective of this study is to estimate and compare the internal energy distributions of different ions (different nature, degree of freedom ‘DOF’ and fragmentations) produced in an electrospray source (ESI) of a triple‐quadrupole instrument (Quattro I Micromass). These measurements were performed using both the Survival Yield method (as proposed by De Pauw) and the MassKinetics software (kinetic model introduced by Vékey). The internal energy calibration is the preliminary step for ESI and collision‐induced dissociation (CID) spectra calculation. meta‐Methyl‐benzylpyridinium ion and four protonated peptides (YGGFL, LDIFSDF, LDIFSDFR and RLDIFSDF) were produced using an electrospray source. These ions were used as thermometer probe compounds. Cone voltages (Vc) were linearly correlated with the mean internal energy values () carried by desolvated ions. These mean internal energy values seem to be slightly dependent on the size of the studied ion. ESI mass spectra and CID spectra were then simulated using the MassKinetics software to propose an empirical equation for the mean internal energy () versus cone voltage (Vc) for different source temperatures (T): < Eint > = [405 × 10−6 − 480 × 10−9 (DOF)] VcT + Etherm(T). In this equation, the Etherm(T) parameter is the mean internal energy due to the source temperature at 0 Vc. Copyright © 2007 John Wiley & Sons, Ltd.
Structural characterizations of lipids A by MS/MS of doubly charged ions on a hybrid linear ion trap/orbitrap mass spectrometer
Authors: Silipo Alba , De Castro Cristina , Lanzetta Rosa , Molinaro Antonio , Parrilli Michelangelo , Vago Giorgio , Sturiale Luisa , Messina Angela , Garozzo Domenico
Published: November 2007

Here, a new ‘one pot’ and fast approach is described, based on electrospray ionization (ESI) of negative ions by using a hybrid linear ion trap/orbitrap mass spectrometer (LTQ/orbitrap) for MS and MS/MS analysis. By this method the distribution of the primary and secondary acyl residues of the intact lipid A is inferred by analysis of the ESI spectra measured in positive and negative mode. The analysis of these data allows an unequivocal assignment of the fatty acid distribution. This methodology was successfully tested on two different lipid A with known structures, deriving from the Agrobacterium tumefaciens and Escherichia coli lipopolysaccharides (LPS). Copyright © 2007 John Wiley & Sons, Ltd.
A flow injection electrospray ionization tandem mass spectrometric method for the simultaneous measurement of trimethylamine and trimethylamine N‐oxide in urine
Authors: Johnson David W.
Published: November 2007

Key metabolites for the diagnosis of the genetic disorder trimethylaminuria are trimethylamine (TMA) and trimethylamine N‐oxide (TMAO). A rapid, automatable flow injection ESI‐MS/MS method for their measurement in urine has been developed. The TMA was derivatized with ethyl bromoacetate to form ethyl betaine bromide. The 2 min ESI‐MS/MS analysis employed four multiple reaction monitoring (MRM) ion pairs for derivatized TMA (146.1, 118.1), derivatized 2H9‐TMA (155.1, 127.1), TMAO (76.1, 58.1) and 2H9‐TMAO (85.1, 66.1). In control urine samples (n = 27) referred for suspected metabolic problems TMA was 0.11–1.19 mmol/mol creatinine, TMAO was 13.5–181 mmol/mol creatinine and the TMA/TMAO ratio was 0.0025–0.055. In five patients with diagnosed trimethylaminuria, TMA was 5.3–230 mmol/mol creatinine, TMAO was 0.36–607 mmol/mol creatinine and the TMA/TMAO ratio was 0.20–134. Copyright © 2007 John Wiley & Sons, Ltd.
Neural progenitor cells transplanted into the uninjured brain undergo targeted migration after stroke onset
Authors: Guzman Raphael , Bliss Tonya , De Los Angeles Alejandro , Moseley Mike , Palmer Theo , Steinberg Gary
Published: November 2007

Endogenous neural stem cells normally reside in their niche, the subventricular zone, in the uninjured rodent brain. Upon stroke, these cells become more proliferative and migrate away from the subventricular zone into the surrounding parenchyma. It is not known whether this stroke‐induced behavior is due to changes in the niche or introduction of attractive cues in the infarct zone, or both. A related question is how transplanted neural stem cells respond to subsequent insults, including whether exogenous stem cells have the plasticity to respond to subsequent injuries after engraftment. We addressed this issue by transplanting neural progenitor cells (NPCs) into the uninjured brain and then subjecting the animal to stroke. We were able to follow the transplanted NPCs in vivo by labeling them with superparamagnetic iron oxide particles and imaging them via high‐resolution magnetic resonance imaging (MRI) during engraftment and subsequent to stroke. We find that transplanted NPCs that are latent can be activated in response to stroke and exhibit directional migration into the parenchyma, similar to endogenous neural NPCs, without a niche environment. © 2007 Wiley‐Liss, Inc.
Induction and subcellular localization of high‐mobility group box–1 (HMGB1) in the postischemic rat brain
Authors: Kim Jung‐Bin , Lim Chae‐Moon , Yu Young‐Mi , Lee Ja‐Kyeong
Published: November 2007

High‐mobility group box–1 (HMGB1) was originally identified as a ubiquitously expressed, abundant nonhistone DNA‐binding protein. Recently, it was found to act as a cytokine‐like mediator of delayed endotoxin lethality and of acute lung injury. Previously, we reported that HMGB1 is massively released extracellularly and plays a cytokine‐like function in the postischemic brain. In the present study, we examined the expression profile and cellular distribution of HMGB1 in rat brain after transient focal cerebral ischemia. The expression of HMGB1 in infarction areas in the ipsilateral sides gradually declined over 2 days after 1 hr of middle cerebral artery occlusion (MCAO) to below the basal level. However, after 3 days of reperfusion, HMGB1 level increased to above the basal level, especially in infarction cores, and this delayed induction was then maintained for several days. Immunohistochemistry using a polyclonal antibody against HMGB1 revealed its detailed expression pattern and subcellular localization in the postischemic brain. HMGB1 was found to be widely expressed throughout the normal brain and to be localized to the nuclei of almost all neurons and oligodendrocyte‐like cells. After 1 hr of MCAO, HMGB1 immediately translocated from the neuron nuclei to the cytoplasm and subsequently was depleted from neurons during the excitotoxicity‐induced acute damaging process. Moreover, beginning 2 days after reperfusion, HMGB1 was notably induced in activated microglia, astrocytes, and in microvascular structures, and these delayed gradual inductions were sustained for several days. These findings suggest that HMGB1 functions as a cytokine‐like mediator in a paracrine and autocrine manner in the postischemic brain. © 2007 Wiley‐Liss, Inc.
Sorting signals and regulation of cognate basolateral trafficking in myelin biogenesis
Authors: Klunder Bert , Baron Wia , Schrage Cobi , de Jonge Jenny , de Vries Hans , Hoekstra Dick
Published: November 2007

A detailed understanding of trafficking pathways in mature oligodendrocytes is essential for addressing issues aimed at controlling (re)myelination by modulating myelin‐directed transport. Previously, we have shown that viral marker proteins HA and VSV G, on reaching the apical and basolateral surfaces of polarized epithelial cells, respectively, are primarily transported to the plasma membrane and myelin sheet, respectively, in oligodendrocytes (OLGs). In the present study, we demonstrated that in OLGs basolateral sorting signals similar to those in epithelial cells may target proteins to the myelin sheet, emphasizing the basolateral‐ and apical‐like nature of the myelin sheet and plasma membrane, respectively. Thus, substitution of essential amino acids reverses the direction of targeting of these proteins, whereas elimination of apical targeting of HA coincides with its dissipation from detergent‐resistant microdomains. Furthermore, protein kinase C activation negatively regulated transport of the OLG resident transmembrane protein PLP to the myelin sheet, like that of VSV G as shown previously, but did not affect the localization of the membrane‐associated myelin‐specific proteins MBP and CNP. These data imply that several distinctly regulated pathways operate in myelin sheet directed–transport that at least partly rely on a cognate basolateral sorting signal. © 2007 Wiley‐Liss, Inc.
Nicotinic acetylcholine receptor‐subunit mRNAs in the mouse superior cervical ganglion are regulated by development but not by deletion of distinct subunit genes
Authors: Putz G. , Kristufek D. , Orr‐Urtreger A. , Changeux J.‐P. , Huck S. , Scholze P.
Published: November 2007

Mice with deletions of nicotinic ACh receptor (nAChR) subunit genes are valuable models for studying nAChR functions. We could previously show in the mouse superior cervical ganglion (SCG) that the absence of distinct subunits affects the functional properties of receptors. Here, we have addressed the question of whether deletions of the subunits α5, α7, or β2 are compensated at the mRNA level, monitored by reverse transcription and quantitative real‐time polymerase chain reaction. Relative to our reference gene, α3, which is expressed in all SCG nAChRs, mRNA levels of β4 showed little change from birth until adult ages in intact ganglia of wild‐type mice. In contrast, α4 declined sharply after birth and was barely detectable in adult animals. α5, α7, and β2 subunit message levels also declined, though more slowly and less completely than α4. The subunits α6 and β3 were detected by conventional polymerase chain reaction at very low levels, if at all, whereas α2 was never seen in any of our samples. The developmental profile of nAChR mRNA levels in the three knockout strains did not differ markedly from that of wild‐type mice. Likewise, message levels of nAChR subunits were similar in cultures prepared from either wild‐type or knockout animals. Our observations indicate a developmental regulation of nAChR subunit mRNAs in the SCG of mice after birth that was not affected by the three knockouts under investigation. © 2007 Wiley‐Liss, Inc.
Neuregulin‐1 induces acetylcholine receptor transcription in the absence of GABPα phosphorylation
Authors: Herndon Carter A. , Fromm Larry
Published: November 2007

Localization of acetylcholine receptors (AChRs) to the postsynaptic region of muscle is mediated in part by transcriptional mechanisms, because the genes encoding AChR subunits are transcribed selectively in synaptic myofiber nuclei. Neuregulin‐1 (NRG‐1) is a synaptic signal and induces transcription of AChRs in muscle cells. Signaling by NRG‐1 is thought to involve the transcription factor GA‐binding protein (GABP), a heterodimer of GABPα, which is a member of the Ets family, and GABPβ. Phosphorylation of certain other Ets proteins outside the Ets DNA‐binding domain serves to stimulate transcriptional activation in response to extracellular signals. According to previous studies, NRG‐1 stimulates phosphorylation of GABPα at threonine 280 in the N‐terminal region adjacent to the Ets domain, suggesting that GABPα phosphorylation might contribute to NRG‐1 responsiveness. To determine the functional importance of the N‐terminal region of GABPα and whether its function is regulated by phosphorylation, we generated muscle cell lines in which the endogenous GABPα gene was deleted and replaced by variants of GABPα mutated in the N‐terminal region. We found that NRG‐1 can induce transcription in cells with mutated T280 phosphorylation site, indicating that T280 phosphorylation does not contribute to NRG‐1 responsiveness. We also found that NRG‐1‐induced transcription occurs in cells missing the entire N‐terminal region of GABPα. Because NRG‐1 signaling is not expected to alter the function of the C‐terminal region, which remains in these cells, these results suggest that GABPβ, or other interacting components, rather than GABPα directly, is targeted by NRG‐1 signaling. © 2007 Wiley‐Liss, Inc.
Reduction of wear volume from ultrahigh molecular weight polyethylene knee components by the addition of vitamin E
Authors: Teramura Satoshi , Sakoda Hideyuki , Terao Tomohiro , Endo Miguel M. , Fujiwara Kunihiko , Tomita Naohide
Published: November 2007

Wear performance and debris‐size distribution of vitamin E (DL‐α tocopherol, VE)‐added ultrahigh molecular weight polyethylene (UHMWPE) was evaluated using a knee‐simulator test. VE was mixed with GUR 1050 UHMWPE powder at 0.3 wt%, and the tibial components of the knee joint were made by direct compression molding. The VE‐added UHMWPE showed consistently lower wear volume throughout the test. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:460–464, 2008
Stimulation of nitric oxide mechanotransduction in single osteoblasts using atomic force microscopy
Authors: McGarry James G. , Maguire Paula , Campbell Veronica A. , O'Connell Brian C. , Prendergast Patrick J. , Jarvis Suzanne P.
Published: November 2007

Nitric oxide (NO) released from mechanosensitive bone cells plays a key role in the adaptation of bone structure to its mechanical usage. Despite its importance in bone, the mechanisms involved in NO mechanotransduction at the cellular level remain unknown. Using combined atomic force microscopy and fluorescence microscopy, we report both stimulation and real‐time monitoring of NO responses in single osteoblasts induced by application of quantified periodic indenting forces to the osteoblast membrane. Peak forces ranging from 17 to 50 nN stimulated three distinct NO responses in the indented osteoblasts: (1) a rapid and sustained diffusion of NO from the perinuclear region, (2) diffusion of NO from localized pools throughout the osteoblast, and (3) an initial increase and subsequent drop in intracellular NO. Force‐indentation characteristics showed considerable interosteoblast variation in elasticity. NO responses were associated with application of force to more rigid membrane sites, suggesting cytoskeletal involvement in mechanotransduction. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:513–521, 2008
Effects of different molecular weight hyaluronan products on the expression of urokinase plasminogen activator and inhibitor and gelatinases during the early stage of osteoarthritis
Authors: Hsieh Yih‐Shou , Yang Shun‐Fa , Lue Ko‐Huang , Chu Shu‐Chen , Lu Ko‐Hsiu
Published: November 2007

Hyaluronan or hyaluronic acid (HA) has been used to treat osteoarthritic knees for more than 30 years. Here, we tested the hypothesis that HA with high molecular weight (MW) would have greater effects than HA with low MW on the expression of the plasminogen activator (PA)/plasmin system and gelatinases [matrix metalloproteinase (MMP)‐2 and MMP‐9] during early development of osteoarthritis (OA). We compared the levels of MMP‐2, MMP‐9, urokinase‐type PA (u‐PA), and PA inhibitor‐1 (PAI‐1) in a series of chondral, meniscal, and synovial cultures of early OA after treatment with or without three different MW HA products (Hyalgan and Artz with low MW, and Synvisc with high MW). Gelatin zymography revealed that three different HA products could decrease the secretion of MMP‐2 in all tissue cultures and MMP‐9 in meniscal and synovial cultures time‐dependently. Enzyme‐linked immunosorbent assay showed that Artz and Synvisc had significant inhibition on u‐PA and PAI‐1 levels after 24 h, but Hyalgan did at 96 h. Compared with Hyalgan and Artz, Synvisc provided the greatest ability to inhibit MMP‐2, MMP‐9, u‐PA, and PAI‐1 expression. Our studies clearly demonstrate that the therapeutic effects of using HA to treat early OA may be partially dependant on downregulation of the PA/plasmin system and gelatinases expression, which delay the structural progression of the disease. HA with high MW might have a greater ability than that with low MW to offer effective protection for articular cartilage. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:475–484, 2008
Web‐based destination marketing systems: assessing the critical factors for management and implementation
Authors: Wang Youcheng
Published: November 2007

The Web‐based destination marketing system (DMS) has been widely used as a distribution channel and marketing tool by destination marketing organisations (DMOs) at different levels in the promotion and management of tourism destinations. However, successful Web marketing requires a systematic approach in understanding key factors supporting the management and implementation of the DMS both from business and technical perspectives. The purpose of this study is to assess the critical factors of the Web‐based DMS used by DMOs in the USA on the following five areas: website function design, website promotion, Website‐performance measurement, Web‐marketing impact assessment and organisation technology environment. Discussions of the study results and implications for Internet destination marketing and management are also provided. Copyright © 2007 John Wiley & Sons, Ltd.
Distillery marketing and the visitor experience: a case study of Scottish malt whisky distilleries
Authors: McBoyle Geoff , McBoyle Edith
Published: November 2007

Since the 1960s, visitor tours of Scottish malt whisky distilleries have been used by whisky companies to promote their products. The original concept of the visitor as passive observer has evolved to include the notion of visitor as VIP guest in three special interest attractions—connoisseur tours, whisky schools and the Classic Malts Cruise. A value‐attainment construct based on a means–end chain progression is used to illustrate the linkage between distillery attributes and the enhancement of higher values in visitors in the three attractions. Service quality is suggested as a key component of the attractions' success. Copyright © 2007 John Wiley & Sons, Ltd.
Gaining residents' support for tourism and planning
Authors: Oviedo‐Garcia M. Angeles , Castellanos‐Verdugo Mario , Martin‐Ruiz David
Published: November 2007

This research analyses residents' perceptions of the effects of tourism. Economic, cultural and environmental effects are identified as determinants of residents' attitudes towards tourism development and planning. Authors speculate that there are different patterns of resident's support depending on their differential benefits obtained from tourism. A conceptual model is developed and empirically tested in Santiponce, a small community in southern Spain. Our results support our basic hypothesis: resident's level of personal benefits obtained from tourism influence their perceptions regarding tourism impacts, and in consequence, their support for tourism development and for tourism planning. Copyright © 2007 John Wiley & Sons, Ltd.
Synthesis, Characterization, and Evaluation of Amine‐Terminated Cycloaliphatic‐Substituted Polysiloxanes
Authors: Dworak David P. , Soucek Mark D.
Published: November 2007

Cyclopentyl‐ and cyclohexyl‐substituted polysiloxanes terminated with amino groups were prepared. Initially, the cycloalkene and dichlorosilane were reacted at high pressure (approx. 250 psi) and high temperature (120 °C) to yield the cycloaliphatic dichlorosilane in a two‐step process. Both the mono‐ and disubstituted chlorosilane monomers underwent an oligomerization to produce cyclic oligomers of low molecular weight (≈2 000 g · mol−1). Amine‐terminated polysiloxanes were produced via a base‐catalyzed ring‐opening polymerization of the cyclic oligomers with 1,3‐bis(3‐aminopropyl)tetramethyldisiloxane to yield low molecular weight polysiloxanes (≈9 000 g · mol−1, amine equivalent weight = ≈4 300 g · equiv.−1). The polysiloxanes were characterized by 1H and 29Si NMR, and Fourier transform‐infrared spectroscopy (FT‐IR). The amine‐terminated polysiloxane was mixed with a cycloaliphatic epoxy‐functionalized cycloaliphatic polysiloxane in order to produce crosslinked epoxy–amine films. The mechanical and physical properties of the film were evaluated and afford a glass transition of the material was 29.5 ± 0.7 °C for the cyclopentyl‐substituted polysiloxane and 38.6 ± 0.7 °C for the cyclohexyl‐substituted polysiloxane. Evaluation of pull‐off adhesion indicated that 0.5 MPa of normal force was required to remove the epoxy/amine film from an aluminum substrate.

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Model Reaction Studies and Crosslinking of Dimethyl‐meta‐isopropenylbenzyl Isocyanate Containing Ambient Crosslinkable Latex
Authors: Yoon Jihwan , Lovell Peter A.
Published: November 2007

The mechanism of TMI‐induced crosslinking was studied using model reactions in a mixture of TMI, water and acetic acid. The hydrolysis of TMI was slow at room temperature, but could be enhanced by the incorporation of carboxylic acid groups. The formation of amide linkages via condensation between TMI and carboxylic acid groups did occur at room temperature, but was very slow. The crosslinking of a fully crosslinked latex film was also studied using a new type of latex. The degree of crosslinking of the core‐crosslinked latex films was lower than theoretical values and the mechanical properties were poor, which was ascribed to insufficient interfacial crosslinking.

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Self‐Assembling Nanomaterials using Magnetic Nanoparticles Modified with Polystyrene Brushes
Authors: García Ignacio , Tercjak Agnieszka , Zafeiropoulos Nikolaos E. , Stamm Manfred , Mondragon Iñaki
Published: November 2007

Magnetic nanomaterials have been studied in order to generate novel nanocomposites that display both the magnetic properties of the nanoparticles and the ability to self‐assemble of the amorphous block copolymer matrix. Towards this goal, iron oxide magnetic nanoparticles have been modified with PS brushes by ATRP in order to improve both the dispersion and the affinity of the nanoparticles with one of the blocks of a polystyrene‐block‐polybutadiene‐block‐polystyrene block copolymer. This method of preparation of nanocomposites opens new strategies for the generation of magnetic nanomaterials. The samples are characterized using DSC and atomic and magnetic force microscopies.

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Informatics development: Challenges and solutions for MALDI mass spectrometry
Authors: Fenyö David , Beavis Ronald C.
Published: November 2007

Matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) has been successfully applied to elucidating biological questions trough the analysis of proteins, peptides, and nucleic acids. Here, we review the different approaches for analyzing the data that is generated by MALDI‐MS. The first step in the analysis is the processing of the raw data to find peaks that correspond to the analytes. The peaks are characterized by their areas (or heights) and their centroids. The peak area can be used as a measure of the quantity of the analyte, and the centroid can be used to determine the mass of the analyte. The masses are then compared to models of the analyte, and these models are ranked according to how well they fit the data and their significance is calculated. This allows the determination of the identity (sequence and modifications) of the analytes. We show how this general data analysis workflow is applied to protein and nucleic acid chemistry as well as proteomics. © 2007 Wiley Periodicals, Inc., Mass Spec Rev 27:1–19, 2008
HIV‐1 integrase inhibitors: 2005–2006 update
Authors: Dayam Raveendra , Gundla Rambabu , Al‐Mawsawi Laith Q. , Neamati Nouri
Published: November 2007

HIV‐1 integrase (IN) catalyzes the integration of proviral DNA into the host genome, an essential step for viral replication. Inhibition of IN catalytic activity provides an attractive strategy for antiretroviral drug design. Currently two IN inhibitors, MK‐0518 and GS‐9137, are in advanced stages of human clinical trials. The IN inhibitors in clinical evaluation demonstrate excellent antiretroviral efficacy alone or in combination regimens as compared to previously used clinical antiretroviral agents in naive and treatment‐experienced HIV‐1 infected patients. However, the emergence of viral strains resistant to clinically studied IN inhibitors and the dynamic nature of the HIV‐1 genome demand a continued effort toward the discovery of novel inhibitors to keep a therapeutic advantage over the virus. Continued efforts in the field have resulted in the discovery of compounds from diverse chemical classes. In this review, we provide a comprehensive report of all IN inhibitors discovered in the years 2005 and 2006. © 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 1, 118–154, 2008
Purification and characterization of natural Bet v 1 from birch pollen and related allergens from carrot and celery
Authors: Bollen Mirko A. , Garcia Aranzazu , Cordewener Jan H. G. , Wichers Harry J. , Helsper Johannes P. F. G. , Savelkoul Huub F. J. , van Boekel Martinus A. J. S.
Published: November 2007

Birch pollen allergy is predominantly caused by the major allergen Bet v 1 and can lead to crossreactions with homologous proteins in food. Two major cross‐reactive food allergens are Dau c 1 from carrot and Api g 1 from celery, which have never been purified from their natural source. Here, we describe a non‐denaturing purification method for obtaining natural Bet v 1, Dau c 1 and Api g 1, comprising of ammonium sulfate precipitation, hydrophobic interaction chromatography and size exclusion chromatography. This method resulted in 98–99% pure isoform mixtures for each allergen. Characterization of these isoform mixtures with Q‐TOF MS/MS clearly showed earlier reported isoforms of Bet v 1, Dau c 1 and Api g 1, but also new isoforms. The presence of secondary structure in the three purified allergens was demonstrated via circular dichroism and showed high similarity. The immune reactivity of the natural allergens was compared with recombinant proteins by Western blot and ELISA and showed similar reactivity.
Prostaglandin E synthase 2 (PTGES2) Arg298His polymorphism and parameters of the metabolic syndrome
Authors: Lindner Inka , Helwig Ulf , Rubin Diana , Fischer Alexandra , Marten Berit , Schreiber Stefan , Döring Frank , Schrezenmeir Jürgen
Published: November 2007

The prostaglandin E synthase 2 (PTGES2) gene maps to a locus linked to obesity and is involved in the synthesis of the antilipolytic compound prostaglandin E2. In a recent study, we found an association of the minor PTGES2 Arg298His allele and lower risk of type 2 diabetes mellitus in the European Investigation into Cancer and Nutrition (EPIC) and Cooperative Health Research in the Augsburg Region (KORA) cohorts. Here, we employed our Metabolic Intervention Cohort Kiel (MICK) to assess the influence of the PTGES2 Arg298His polymorphism on a wider scale of parameters of the metabolic syndrome and postprandial metabolism. In comparison to subjects homozygous for the Arg allele, carriers of the His‐allele showed significantly lower fasting insulin (geometric mean ± SEM: 11.8 μU/mL, 11.41–12.25 versus 13.0, 12.71–13.33; p = 0.023), lower postprandial insulin levels after an oral glucose tolerance test (area under the curve 77.2, 74.07–80.52 versus 81.2, 78.8–83.63; p = 0.023) and lower homeostasis model assessment (HOMA)‐insulin‐resistance (3.030, 2.909–3.157 versus 3.346, 3.257–3.438; p = 0.041) and HOMA‐β‐cell‐function (107.2, 104.04–110.52 versus 117.2, 114.65–119.71; p = 0.019). Adjustment for body mass index (BMI) resulted in a loss of these significant differences. BMI tended to show lower values in His‐allele carriers, (p = 0.067). In conclusion, risk‐reducing effects of the minor His allele of the PTGES2 Arg298His polymorphism could be mediated partly by lowered BMI.
Recognizing the role of parents in developmental outcomes: A systems approach to evaluating the child with developmental disabilities
Authors: Head Lara S. , Abbeduto Leonard
Published: November 2007

When developmental concerns arise in children, a clinical assessment focuses on the child's developmental profile to achieve three goals (1) determine diagnosis, (2) develop interventions, and (3) evaluate progress. Parents often have needs during this time that are not addressed by professionals because of the exclusive focus on the child during the evaluation. In this article, we suggest that clinicians take a “systems” approach to the assessment process by recognizing how the well being of family members can impact a child with a developmental disability. We review systems theory and its conceptualization of individual functioning and discuss how parental well‐being differs according to child diagnosis. Finally we suggest a systems‐based model to use during the assessment process. © 2007 Wiley‐Liss, Inc. MRDD Research Reviews 2007;13:293–301.
Expressed emotion in families of children and adults with intellectual disabilities
Authors: Hastings Richard P. , Lloyd Tracey
Published: November 2007

Expressed emotion (EE) is a measure of the affective relationship between two people characterized by criticism, hostility, and emotionally over‐involved attitudes. Outside of the field of intellectual disabilities, there has been considerable interest in EE as an environmental marker that explains variance in the severity and/or course of a number of psychiatric disorders. Researchers have also studied EE in parents and found strong associations with children's behavior problems. In this review, we focus on the data from 11 published studies of EE in families of children and adults with intellectual disabilities. We conclude that there is evidence for the presence of high EE in some families, and that this alone should concern researchers and clinicians and set an agenda for considerable future research effort. We also note a lack of attention to the measurement of EE in intellectual disability. In terms of the existing evidence base, we suggest that there is support for the hypothesis that behavior problems in children and adults with intellectual disabilities may be related to high EE in parents, and a small amount of data predicting over time support the putative causal effect of high EE on maintaining or exacerbating behavior problems. Given that EE is perhaps best conceptualized as the result of an interaction between caregivers and those cared for, there is a need to explore interventions that may help to remediate high EE within families. It is also important to understand from this position that EE may be a normative part of the experience ofcaring for someone under very stressful circumstances and not something for which families are blamed. Other future research priorities and some implications for practice are also discussed. © 2007 Wiley‐Liss, Inc. MRDD Research Reviews 2007;13:339–345.
Meta‐analysis of family‐centered helpgiving practices research
Authors: Dunst Carl J. , Trivette Carol M. , Hamby Deborah W.
Published: November 2007

A meta‐analysis of 47 studies investigating the relationship between family‐centered helpgiving practices and parent, family, and child behavior and functioning is reported. The studies included more than 11,000 participants from seven different countries. Data analysis was guided by a practice‐based theory of family‐centered helpgiving that hypothesized direct effects of relational and participatory helpgiving practices on self‐efficacy beliefs and parent, family, and child outcomes. Results showed that the largest majority of outcomes were related to helpgiving practices with the strongest influences on outcomes most proximal and contextual to help giver/help receiver exchanges. Findings are placed in the context of a broader‐based social systems framework of early childhood intervention and family support. © 2007 Wiley‐Liss, Inc. MRDD Research Reviews 2007;13:370–378.
A numerical method for the one‐dimensional sine‐Gordon equation
Authors: Bratsos A.G.
Published: November 2007

A numerical method based on a predictor–corrector (P‐C) scheme arising from the use of rational approximants of order 3 to the matrix‐exponential term in a three‐time level recurrence relation is applied successfully to the one‐dimensional sine‐Gordon equation, already known from the bibliography. In this P‐C scheme a modification in the corrector (MPC) has been proposed according to which the already evaluated corrected values are considered. The method, which uses as predictor an explicit finite‐difference scheme arising from the second order rational approximant and as corrector an implicit one, has been tested numerically on the single and the soliton doublets. Both the predictor and the corrector schemes are analyzed for local truncation error and stability. From the investigation of the numerical results and the comparison of them with other ones known from the bibliography it has been derived that the proposed P‐C/MPC schemes at least coincide in terms of accuracy with them. © 2007 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2008
Use of radial basis functions for solving the second‐order parabolic equation with nonlocal boundary conditions
Authors: Dehghan Mehdi , Tatari Mehdi
Published: November 2007

Nonlocal mathematical models appear in various problems of physics and engineering. In these models the integral term may appear in the boundary conditions. In this paper the problem of solving the one‐dimensional parabolic partial differential equation subject to given initial and nonlocal boundary conditions is considered. These kinds of problems have certainly been one of the fastest growing areas in various application fields. The presence of an integral term in a boundary condition can greatly complicate the application of standard numerical techniques. As a well‐known class of meshless methods, the radial basis functions are used for finding an approximation of the solution of the present problem. Numerical examples are given at the end of the paper to compare the efficiency of the radial basis functions with famous finite‐difference methods. © 2007 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2008
Validation of ICD‐9 codes with a high positive predictive value for incident strokes resulting in hospitalization using Medicaid health data
Authors: Roumie Christianne L. , Mitchel Edward , Gideon Patricia S. , Varas‐Lorenzo Cristina , Castellsague Jordi , Griffin Marie R.
Published: November 2007

Purpose

To validate ICD 9 codes with a high positive predictive value (PPV) for incident strokes. The study population consisted of Tennessee Medicaid enrollees aged from 50 to 84 years.

Methods

We identified all patients who were hospitalized with a discharge diagnosis of stroke between 1999 and 2003 using highly specific codes (ischemic stroke ICD 9‐CM codes 433.x1, 434 [excluding 434.x0], or 436; intracerebral hemorrhage [431]; and subarachnoid hemorrhage [430]). We reviewed medical records of a systematic sample of 250 cohort members. We randomly selected 10–30 eligible records for review from hospitals with at least 10 stroke hospitalizations.

Results

We reviewed 231 charts (93% of total sampled), and 205 (89%) met study criteria for new outpatient stroke. Of the 205 confirmed new outpatient strokes, 196 had stroke listed as the primary discharge diagnosis (PPV = 96%). However, 46 (23%) of the 196 patients identified by the primary diagnosis also had a remote stroke history (recurrent stroke not incident). Thus the PPV of the primary discharge diagnosis for identifying incident stroke decreased to 74%. When we applied an algorithm that restricted our population to those with stroke as the primary diagnosis and excluded patients with any prior outpatient diagnosis of stroke, we identified incident stroke events with more precision (PPV = 80%).

Conclusion

The PPV of incident strokes was 80% using our strategy of primary discharge diagnosis and excluding prior outpatient diagnoses of stroke. Although an unknown percentage of incident strokes are missed, this group of proven incident stroke patients can be used for etiologic studies of medication exposures. Copyright © 2007 John Wiley & Sons, Ltd.
Molecular, rheological, and crystalline properties of low‐density polyethylene in blown film extrusion
Authors: Majumder Khokan Kanti , Hobbs Graham , Bhattacharya Sati N.
Published: November 2007

The molecular weight and its distribution, degree of long chain branching and cooling rate strongly influence crystallinity during processing, which in turn determines the processability and the ultimate properties of the blown film. Generally a decrease in the number of branches and molecular weight of the polymer and the cooling rate results in an increase of the crystallinity. Length of the main chain and extent of branching in low‐density polyethylene (LDPE) are also factors that affect melt rheology and film crystallinity. Long chain branched polyethylene is suitable in the blown film process due to its better melt strength for bubble stability. The objective of this article is to describe the effect of molecular properties (e.g. molecular weight and its distribution, degree of long chain branching etc) of LDPE on film crystallinity at different cooling rates of blown film extrusion. Two different grades of LDPE were selected to investigate molecular characteristics, crystallinity, and rheology. The resins were processed in a blown film extrusion pilot plant using four different cooling rates. Molecular, rheological, and crystalline properties of the resins were key parameters considered in this study. POLYM. ENG. SCI., 47:1983–1991, 2007. © 2007 Society of Plastics Engineers
Stretching induced phase transformations in melt extruded poly(vinylidene fluoride) cast films: Effect of cast roll temperature and speed
Authors: Mhalgi Milind V. , Khakhar Devang V. , Misra Ashok
Published: November 2007

Melt extruded poly(vinylidene fluoride) cast films were prepared at different cast roll temperatures and speeds to study the effect of casting temperature and preorientation of the melt on the α‐ to β‐phase transformation in these films after uniaxial stretching. X‐ray and fourier transform infrared spectroscopy were used to identify the crystalline phases. The unstretched films were characterized using small angle light scattering (SALS). The films were stretched to a stretch ratio of 4.2 and at 80°C. Birefringence of the films and the fraction of β‐phase [F(β)] formed after uniaxial stretching increased with stretch ratio. The films showed increased crystallinity after stretching. For the films prepared at different cast roll temperatures, there was little change in F(β) in the films having a cast roll temperature between 75 and 120°C, but for the film with a cast roll temperature of 130°C F(β) decreased considerably. For the films prepared at different cast roll speeds, the F(β) increased with stretch ratio as well as with cast roll speed for a fixed stretch ratio. The primary effect of changing both the parameters is a change in the average spherulitic radius (R), in the unstretched films measured using SALS. The F(β) obtained correlated well with R and lower spherulitic radii resulted in the higher conversion to the β‐phase. POLYM. ENG. SCI., 47:1992–2004, 2007. © 2007 Society of Plastics Engineers
Chain extension and degradation during reactive processing of PET in the presence of triphenyl phosphite
Authors: Cavalcanti F.N. , Teófilo E.T. , Rabello M.S. , Silva S.M.L.
Published: November 2007

Poly(ethylene terephthalate) (PET) is chemically degraded during processing and/or using by a number of sources including temperature, humidity, and ultraviolet radiation. As a consequence, a large loss in engineering properties is observed when PET products are recycled. To overcome this problem, various types of chain extenders were developed in an attempt to recover the polymer molecular sizes by chemical reactions during processing. This work investigates the use of triphenyl phosphite (TPP) as a chain extender of virgin and recycled PET. Compounds with 1 and 3% of TPP were prepared and processed under various conditions using a torque rheometer. An increase in torque during mixing was associated with chain extension reactions whereas the observed decrease in torque afterwards was due to chemical degradation. The optimum processing conditions were reached (260°C, 1% chain extender), with a maximum in chain extension and a minimum in subsequent degradation. An important finding of this work was that the chemical degradation of chain extended PET occurs very easily during storage and it was considered to be a result of the influence of by‐products of TPP reaction with PET. The extraction of these products with acetone was shown to be quite effective, with a considerable stability during storage. This work also showed that the recycled PET is much less able to react with TPP in comparison with the virgin polymer. POLYM. ENG. SCI., 47:2155–2163, 2007. © 2007 Society of Plastics Engineers