bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of 3‐(Tosylalkyl)indazoles and their Desulfonylation Reactions – A New Entry to 3‐Substituted Indazoles by an Unprecedented Friedel–Crafts Process
Authors: Campetella Silvia , Palmieri Alessandro , Petrini Marino
Published: May 2009

Reaction of indazoles with aldehydes in the presence of p‐toluenesulfinic acid affords the corresponding sulfonyl indazoles in satisfactory yields. The reported Friedel–Crafts process is rather unusual on indazoles because of the reduced electronic density of the heterocycle. The obtained sulfonyl indazoles can be desulfonylated under reductive conditions, finally leading to 3‐alkylated indazoles.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
A Third‐Generation Hydrogen Peroxide Biosensor Based on Horseradish Peroxidase Covalently Immobilized on Electrografted Organic Film on Screen‐Printed Carbon Electrode
Authors: Radi Abd‐Elgawad , Muñoz‐Berbel Xavier , Cortina‐Puig Montserrat , Marty Jean‐Louis
Published: May 2009

A new convenient strategy to fabricate a third‐generation hydrogen peroxide biosensor was described. The screen‐printed carbon electrode (SPCE) was first modified with a layer of 4‐nitrophenyl assembled from the 4‐nitroaniline diazonium salt synthesized in situ in acidic aqueous solution. Next, the nitro groups were converted to amines followed by crosslinking to the horseradish peroxidase (HRP) by glutaraldehyde. The redox chemistry of the active center of the HRP was observed and the HRP‐modified electrode displayed electrocatalytic activity towards the reduction of hydrogen peroxide (H2O2) without any mediators. H2O2 was determined in a linear range from 5.0 μM to 50.0 μM, with a detection limit of 1.0 μM. Furthermore, the biosensor exhibited fast amperometric response, good reproducibility and long‐term stability.
High‐fidelity aerodynamic shape optimization of modern transport wing using efficient hierarchical parameterization
Authors: Morris A. M. , Allen C. B. , Rendall T. C. S.
Published: May 2009

Aerodynamic shape optimization technology is presented, using an efficient domain element parameterization approach. This provides a method that allows geometries to be parameterized at various levels, ranging from gross three‐dimensional planform alterations to detailed local surface changes. Design parameters control the domain element point locations and, through efficient global interpolation functions, deform both the surface geometry and corresponding computational fluid dynamics volume mesh, in a fast, high quality, and robust fashion. This results in total independence from the mesh type (structured or unstructured), and optimization independence from the flow‐solver is achieved by obtaining gradient information for an advanced gradient‐based optimizer by finite‐differences. Hence, the optimization tool can be used in conjunction with any flow‐solver and/or mesh generator. Results have been presented recently for two‐dimensional aerofoil cases, and shown impressive results; drag reductions of up to 45% were demonstrated using only 22 active design parameters. This paper presents the extension of these methods to three dimensions, with results for highly constrained optimization of a modern aircraft wing in transonic cruise. The optimization uses combined global and local parameters, giving 388 design variables, and produces a shock‐free geometry with an 18% reduction in drag, with the added advantage of significantly reduced root moments. Copyright © 2009 John Wiley & Sons, Ltd.
Dissociable frontal controls during visible and memory‐guided eye‐tracking of moving targets
Authors: Ding Jinhong , Powell David , Jiang Yang
Published: May 2009

When tracking visible or occluded moving targets, several frontal regions including the frontal eye fields (FEF), dorsal‐lateral prefrontal cortex (DLPFC), and anterior cingulate cortex (ACC) are involved in smooth pursuit eye movements (SPEM). To investigate how these areas play different roles in predicting future locations of moving targets, 12 healthy college students participated in a smooth pursuit task of visual and occluded targets. Their eye movements and brain responses measured by event‐related functional MRI were simultaneously recorded. Our results show that different visual cues resulted in time discrepancies between physical and estimated pursuit time only when the moving dot was occluded. Visible phase velocity gain was higher that that of occlusion phase. We found bilateral FEF association with eye‐movement whether moving targets are visible or occluded. However, the DLPFC and ACC showed increased activity when tracking and predicting locations of occluded moving targets, and were suppressed during smooth pursuit of visible targets. When visual cues were increasingly available, less activation in the DLPFC and the ACC was observed. In addition, there was a significant hemisphere effect in DLPFC, where right DLPFC showed significantly increased responses over left when pursuing occluded moving targets. Correlation results revealed that DLPFC, the right DLPFC in particular, communicates more with FEF during tracking of occluded moving targets (from memory). The ACC modulates FEF more during tracking of visible targets (likely related to visual attention). Our results suggest that DLPFC and ACC modulate FEF and cortical networks differentially during visible and memory‐guided eye tracking of moving targets. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Health expenditure estimation and functional form: applications of the generalized gamma and extended estimating equations models
Authors: Hill Steven C. , Miller G. Edward
Published: May 2009

Health‐care expenditure regressions are used in a wide variety of economic analyses including risk adjustment and program and treatment evaluations. Recent articles demonstrated that generalized gamma models (GGMs) and extended estimating equations (EEE) models provide flexible approaches to deal with a variety of data problems encountered in expenditure estimation. To date there have been few empirical applications of these models to expenditures. We use data from the US Medical Expenditure Panel Survey to compare the bias, predictive accuracy, and marginal effects of GGM and EEE models with other commonly used regression models in a cross‐validation study design. Health‐care expenditure distributions vary in the degree of heteroskedasticity, skewness, and kurtosis by type of service and population. To examine the ability of estimators to address a range of data problems, we estimate models of total health expenditures and prescription drug expenditures for two populations, the elderly and privately insured adults. Our findings illustrate the need for researchers to examine their assumptions about link functions: the appropriate link function varies across our four distributions. The EEE model, which has a flexible link function, is a robust estimator that performs as well, or better, than the other models in each distribution. Published in 2009 by John Wiley & Sons, Ltd.
Large liver cell change in hepatitis B virus–related liver cirrhosis #
Authors: Kim Haeryoung , Oh Bong-Kyeong , Roncalli Massimo , Park Chanil , Yoon So-Mi , Yoo Jeong Eun , Park Young Nyun
Published: May 2009

Large liver cell change (LLCC) refers to microscopic lesions often found in various chronic liver diseases; however, its nature is still controversial. Thirty-four formalin-fixed and 19 fresh frozen hepatitis B virus (HBV)-related cirrhosis samples were examined for the presence of LLCC, small liver cell change (SLCC), and hepatocellular carcinoma (HCC). The cell cycle checkpoint status (p21, p27, p16, Tp53), cell dynamics (proliferating cell nuclear antigen, Ki-67, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling, M30), DNA damage (γ-H2AX [H2A histone family, member X]), telomere lengths, chromosomal instability (micronuclei index), and senescence-associated β-galactosidase (SA-β-Gal) activity were evaluated using an in situ approach and compared to those in normal liver (n = 5) and liver with chronic cholestasis (34 cases of hepatolithiasis and three cases of primary biliary cirrhosis). In HBV-related cirrhosis, the p21, p27, and p16 cell cycle checkpoint markers were activated in normal-looking cirrhotic hepatocytes (NLCH), but diminished gradually from LLCC, SLCC, to HCC, with an increase in Tp53 expression. There was a general decrease in telomere length from NLCH, LLCC, SLCC, to HCC. Micronuclei, γ-H2AX foci, and net cellular gain were significantly increased from normal hepatocytes, NLCH, LLCC, SLCC, to HCC. The SA-β-Gal activity was weaker in LLCC compared to NLCH and absent in SLCC and HCC. In contrast, cholestatic LLCC showed retained expression of cell cycle checkpoint markers and decreased net cellular gain compared to adjacent normal-looking hepatocytes. HBV-related LLCC showed significantly higher Tp53 labeling index, γ-H2AX labeling index, and micronuclei index; shorter telomere length; decreased SA-β-Gal activity; and increased net cellular gain compared to cholestatic LLCC. Conclusion: The nature of LLCC is rather heterogeneous depending on the biological setting. The characteristics of HBV-related LLCC are more consistent with dysplastic rather than merely reactive hepatocytes, whereas cholestatic LLCC more likely represents reactive change with more stringent cell cycle checkpoint control. (Hepatology 2009.)
Distinct kinetics and dynamics of cross-presentation in liver sinusoidal endothelial cells compared to dendritic cells #
Authors: Schurich Anna , Böttcher Jan P. , Burgdorf Sven , Penzler Patrick , Hegenbarth Silke , Kern Michaela , Dolf Andreas , Endl Elmar , Schultze Joachim , Wiertz Emmanuel , Stabenow Dirk , Kurts Christian , Knolle Percy
Published: May 2009

Cross-presentation is an important function of immune competent cells, such as dendritic cells (DCs), macrophages, and an organ-resident liver cell population, i.e., liver sinusoidal endothelial cells (LSECs). Here, we characterize in direct comparison to DCs the distinct dynamics and kinetics of cross-presentation employed by LSECs, which promote tolerance induction in CD8 T cells. We found that LSECs were as competent in cross-presenting circulating soluble antigen ex vivo as DCs at a per-cell basis. However, antigen uptake in vivo was 100-fold more pronounced in LSECs, indicating distinct mechanisms of cross-presentation. In contrast to mannose-receptor–mediated antigen uptake and routing into stable endosomes dedicated to cross-presentation in DCs, we observed distinct antigen-uptake and endosomal routing with high antigen turnover in LSECs that resulted in short-lived cross-presentation. Receptor-mediated endocytosis did not always lead to cross-presentation, because immune-complexed antigen taken up by the Fc-receptor was not cross-presented by LSECs, indicating that induction of CD8 T cell tolerance by LSECs is impaired in the presence of preexisting immunity. Conclusion: These results provide a mechanistic explanation how organ-resident LSECs accommodate continuous scavenger function with the capacity to cross-present circulating antigens using distinct kinetics and dynamics of antigen-uptake, routing and cross-presentation compared to DCs. (Hepatology 2009.)
Porcine liver sinusoidal endothelial cells contribute significantly to intrahepatic ammonia metabolism #
Authors: Nedredal Geir I. , Elvevold Kjetil , Ytrebφ Lars M. , Fuskevåg Ole-Martin , Pettersen Ingvild , McCourt Peter A. G. , Bertheussen Kjell , Smedsrφd Bård , Revhaug Arthur
Published: May 2009

Ammonia metabolism in the liver has been largely credited to hepatocytes (HCs). We have shown that liver nonparenchymal cells that include liver sinusoidal endothelial cells (LSECs) produce ammonia. To address the limited knowledge regarding a role for LSECs in ammonia metabolism, we investigated the ammonia metabolism of isolated LSECs and HCs under three different conditions: (1) bioreactors containing LSECs (LSEC-bioreactors), (2) bioreactors containing HCs (HC-bioreactors), and (3) separate bioreactors containing LSECs and HCs connected in sequence (Seq-bioreactors). Our results showed that LSEC-bioreactors released six-fold more ammonia (22.2 nM/hour/106 cells) into the growth media than HC-bioreactors (3.3 nM/hour/106 cells) and Seq-bioreactors (3.8 nM/hour/106 cells). The glutamate released by LSEC-bioreactors (32.0 nM/hour/106 cells) was over four-fold larger than that released by HC-bioreactors and Seq-bioreactors (<7 nM/hour/106 cells). LSEC-bioreactors and HC-bioreactors consumed large amounts of glutamine (>25 nM/hour/106 cells). Glutaminase is known for catalyzing glutamine into glutamate and ammonia. To determine if this mechanism may be responsible for the large levels of glutamate and ammonia found in LSEC-bioreactors, immunolabeling of glutaminase and messenger RNA expression were tested. Our results demonstrated that glutaminase was present with colocalization of an LSEC-specific functional probe in lysosomes of LSECs. Furthermore, using a nucleotide sequence specific for kidney-type glutaminase, reverse-transcription polymerase chain reaction revealed that this isoform of glutaminase was expressed in porcine LSECs. Conclusion: LSECs released large amounts of ammonia, perhaps due to the presence of glutaminase in lysosomes. The ammonia and glutamate released by LSECs in Seq-bioreactors were used by hepatocytes, suggesting an intrahepatic collaboration between these two cell types. (Hepatology 2009.)
Rectal cancer survival in the Nordic countries and Scotland
Authors: Folkesson Joakim , Engholm Gerda , Ehrnrooth Eva , Kejs Anne‐Mette , Påhlman Lars , Harling Henrik , Wibe Arne , Gaard Maria , Þorvaldur Jónsson , Tryggvadottir Laufey , Brewster David H. , Hakulinen Timo , Storm Hans H.
Published: May 2009

The aim of this study was to present detailed population‐based survival estimates for patients with a rectal adenocarcinoma, using cancer register data supplemented with clinical data. Based on cancer register data, differences in rectal cancer survival have been reported between countries in Europe. Variation in the distribution of stage at diagnosis, initial therapy including surgical technique, and comorbidity are possible explanatory factors. Adenocarcinomas in the rectum, diagnosed in 1997 and identified in the national cancer registries in the Nordic countries and Scotland were included. Age standardized 5‐year relative survival and multiplicative regression models for the relative excess mortality were calculated. 3888 patients were included in the survival study. Men in Denmark, Finland and Iceland had lower 5‐year relative survival and poorer stage distribution compared to Norway, Sweden and Scotland. Danish men had the highest rate of excess deaths in the first six months after diagnosis. Stage adjusted, the elevated relative excess mortality decreased and after six months the excess mortality rates were the same in all countries. The poor 5‐year relative survival in Danish men was mainly due to a high excess rate of death during the first six months after diagnosis. The low survival in Finland and Iceland was not in accordance with other periods. For both countries this may be explained by random variation due to small numbers. The study emphasizes the need for high quality and detailed data in order to understand international survival differences, and cautions comparisons between large national samples and those of smaller areas. © 2009 UICC
Stanniocalcin 2 promotes invasion and is associated with metastatic stages in neuroblastoma
Authors: Volland Sonja , Kugler Wilfried , Schweigerer Lothar , Wilting Jörg , Becker Jürgen
Published: May 2009

Stanniocalcin 2 (STC2) is a secreted glycoprotein of as yet unknown functions. We investigated STC2 in human neuroblastoma, the most common solid extra‐cranial tumor of infancy. In primary tumor samples, we found that expression of STC2 is associated with the metastatic Stages 4 and 4s and MYCN expression. In vitro, however, we demonstrate that cell proliferation is reduced by STC2 due to an increase in the basal apoptosis rate of the transfected cells. On the other hand, in vitro assays showed that STC2‐transfected neuroblastoma cells have an increased invasive potential and display higher activity of collagen‐degrading matrix metalloproteinase 2 (MMP2). Using experimental tumors on the chick chorioallantoic membrane (CAM), we observed that STC2 expressing cells show signs of emigration from the solid tumor and destroy blood vessels of the CAM, giving rise to massively bleeding tumors. Erosion of blood vessels was also seen when purified STC2 protein was applied on the CAM. Taken together, we demonstrate a dual role for STC2 in neuroblastoma. It reduces proliferation of tumor cells in vitro, but increases the invasive potential and induces bleeding, and thereby may facilitate early metastasis. The potential of STC2 as a surrogate marker for metastatic neuroblastoma calls for further investigation. © 2009 UICC
Attenuation of proteolysis‐mediated cyclin E regulation by alternatively spliced Parkin in human colorectal cancers
Authors: Ikeuchi Kyoko , Marusawa Hiroyuki , Fujiwara Mikio , Matsumoto Yuko , Endo Yoko , Watanabe Tomohiro , Iwai Akio , Sakai Yoshiharu , Takahashi Ryosuke , Chiba Tsutomu
Published: May 2009

Parkin has a critical role in the ubiquitin‐proteasome system as an E3‐ligase targeting several substrates. Our recent finding that Parkin‐deficient mice are susceptible to tumorigenesis provided evidence that Parkin is a tumor suppressor gene. Dysfunction of the Parkin gene is frequently observed in various human cancers, but the mechanism underlying the cell cycle disruption induced by Parkin dysfunction that leads to carcinogenesis is not known. Here, we demonstrated that Parkin expression in colonic epithelial cells is regulated in a cell cycle‐associated manner. Epidermal growth factor (EGF) stimulation upregulated Parkin gene expression in human colon cells. Inhibition of the phosphoinositide 3‐kinase [PI(3)K]‐Akt‐dependent pathways suppressed growth factor‐induced Parkin expression. The expression of alternatively spliced Parkin isoforms with various deletions spanning exons 3–6 was detected in 18 of 43 (42%) human colorectal cancer tissues. Wild‐type Parkin induced the degradation of cyclin E protein, but the alternatively spliced Parkin identified in colon cancers showed defective proteolysis of cyclin E. These findings indicate that Parkin expression is induced by growth factor stimulation and is involved in the cell cycle regulation of colon cells. Tumor‐specific expression of alternatively spliced Parkin isoforms might contribute to enhanced cell proliferation through the attenuation of proteolysis‐mediated cyclin E regulation in human colorectal cancers. © 2009 UICC
Structure and function of the arolium of Mantophasmatodea (Insecta)
Authors: Eberhard Monika J.B. , Pass Günther , Picker Mike D. , Beutel Rolf , Predel Reinhard , Gorb Stanislav N.
Published: May 2009

All species of the insect order Mantophasmatodea characteristically keep the 5th tarsomere and pretarsus (arolium plus two claws) turned upwards and off the substrate. The unusually large arolium was studied in two species of Mantophasmatodea using bright field light microscopy, reflection microscopy, fluorescence microscopy, TEM, SEM, and Cryo‐SEM. It contains an epithelial gland, numerous tracheoles, and nerves. The gland consists of enlarged epithelial cells with large nuclei, mitochondria, RER, golgi complexes, microtubules, and numerous secretion vesicles. Evidence for exocytosis of the vesicles into the gland reservoir between the epithelial gland and the thick cuticle could be observed. Cryo‐SEM revealed that the ventral side of the arolium and distal part of its dorsal side are covered with a liquid film. Fluid footprints of arolia of individuals walking on a glass plate also indicate the presence of secretory fluid on the arolium surface. Behavioral experiments using animals with ablated arolia showed that representatives of Mantophasmatodea do not need their arolia to detect and respond to vibratory communication signals nor to catch small to medium‐sized prey. Individuals with ablated arolia were not able to move upside down on a smooth glass plate. We conclude that Mantophasmatodea use their arolia for attachment when additional adhesion force is required (e.g. windy conditions, handling large prey, mating). They can bring their arolia in contact with the surface in a very fast reflex (18.0 ± 9.9 ms). The secretory fluid found on the surface is produced by the gland and transported to the outside, presumably through small pore channels, to enhance adhesion to the substrate. J. Morphol., 2009. © 2009 Wiley‐Liss, Inc.
The chemistry of ionized Acetone/Ar mixtures under varying gas flow and mole ratio conditions: A matrix‐isolation study
Authors: Mark Parnis J. , King Kaitlynn A. , Thompson Matthew G. K.
Published: May 2009

The chemistry of ionized acetone : Ar mixtures under varying total gas flow rate and acetone : Ar mole ratio conditions has been studied using matrix‐isolation techniques. Gaseous acetone diluted in excess argon gas was subjected to electron bombardment with 300‐eV electrons. The products of subsequent reaction processes were matrix isolated and analyzed by Fourier transform infrared (FTIR) absorption spectroscopy. Products included 1‐propen‐2‐ol (the enol isomer of acetone), methane, ketene, carbon monoxide, ethane, ethene, acetylene and tricarbon monoxide. Variations in the total flow rate of gas resulted in changes in the efficiency of product formation without significant changes in the relative amounts of the major species formed. Variations in the acetone : Ar mole ratio at fixed total gas flow resulted in striking variations in the products formed, demonstrating a shift from single acetone molecule‐derived charge‐transfer ionization chemistry at low acetone mole ratios, to processes consistent with the participation of two or more acetone molecules at intermediate mole ratios. These results are interpreted in the context of ion‐molecule reaction processes, the onset of which occurs at intermediate acetone mole ratios. Ethane dehydrogenation products are proposed to result from product secondary ionization, a process that is prevalent at high ionizing electron fluxes. Copyright © 2008 John Wiley & Sons, Ltd.
Rhinovirus enhances various bacterial adhesions to nasal epithelial cells simultaneously
Authors: Wang Jong Hwan , Kwon Hyun Ja , Jang Yong Ju
Published: May 2009

Objectives/Hypothesis:

Viral upper respiratory tract infections are often followed by secondary bacterial infections in the form of acute rhinosinusitis. We investigate the effect of rhinovirus infection on the expression of cell adhesion molecules and bacterial adherence to primary human nasal epithelial cells.

Methods:

Cells were infected with rhinovirus serotype 16 (RV‐16), and then Staphylococcus aureus, Streptococcus pneumoniae, or Hemophilus influenzae were added to the culture. Rhinovirus‐induced expression of fibronectin, platelet‐activating factor receptor, and carcinoembryonic antigen‐related cell adhesion molecule, was assayed by confocal microscopy, real‐time polymerase chain reaction, and Western blot analysis. Bacterial adhesion to cells was assessed by confocal microscopy and the fluorescence intensity of adherent bacteria was analyzed using Image‐Pro Plus 5.1 (Media Cybernetics, Inc., Bethesda, MD).

Results:

RV‐16 infection significantly increased the gene and protein expression of fibronectin, platelet‐activating factor receptor, and carcinoembryonic antigen‐related cell adhesion molecule in nasal epithelial cells. Compared with rhinovirus‐uninfected control cells, the adhesion of S. aureus, S. pneumoniae, and H. influenzae increased significantly to 2.53‐fold, 1.51‐fold, and 2.74‐fold of control levels, respectively, in rhinovirus‐infected nasal epithelial cells.

Conclusions:

These findings suggest that increased expression of host cell adhesion molecules may be the mechanism accounting for the increase in susceptibility to bacterial rhinosinusitis associated with rhinovirus‐induced upper respiratory infections. Laryngoscope, 2009
Glucose Responsive Hydrogel Networks Based on Protein Recognition
Authors: Ehrick Jason D. , Luckett Matthew R. , Khatwani Santoshkumar , Wei Yinan , Deo Sapna K. , Bachas Leonidas G. , Daunert Sylvia
Published: May 2009

Stimuli‐responsive materials capable of manifesting physical changes in response to environmental signals are valuable tools for use in a variety of biomedical applications. Herein we describe one such smart glucose‐responsive hydrogel material prepared by immobilizing the glucose/galactose binding protein within an acrylamide hydrogel network. This hydrogel demonstrates a quantitative “accordion”‐like dynamic response in the presence of glucose. We further show the feasibility of employing this responsive smart material as a gating agent for controlled drug delivery, thus, demonstrating that these hydrogels may eventually lead to the development of implantable drug delivery systems for diabetes management applications.

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Modulation of Osteogenic Differentiation of Human Mesenchymal Stem Cells by Poly[(L‐lactide)‐co‐(ε‐caprolactone)]/Gelatin Nanofibers
Authors: Rim Nae Gyune , Lee Ji Hye , Jeong Sung In , Lee Bu Kyu , Kim Chun Ho , Shin Heungsoo
Published: May 2009

Developing biomaterial scaffolds to elicit specific cell responses is important in many tissue engineering applications. We hypothesized that the chemical composition of the scaffold may be a key determinant for the effective induction of differentiation in human mesenchymal stem cells (hMSCs). In this study, electrospun nanofibers with different chemical compositions were fabricated using poly[(L‐lactide)‐co‐(ε‐caprolactone)] (PLCL) and gelatin. Scanning electron microscopy (SEM) images showed a randomly arranged structure of nanofibers with diameters ranging from 400 nm to 600 nm. The incorporation of gelatin in the nanofibers stimulated the adhesion and osteogenic differentiation of hMSCs. For example, the well‐stretched and polygonal morphology of hMSCs was observed on the gelatin‐containing nanofibers, while the cells cultured on the PLCL nanofibers were contracted. The DNA content and alkaline phosphatase activity were significantly increased on the PLCL/gelatin blended nanofibers. Expression of osteogenic genes including alkaline phosphatase (ALP), osteocalcin (OCN), and collagen type I‐α2 (Col I‐α2) were also upregulated in cells cultured on nanofibers with gelatin. Mineralization of hMSCs was analyzed by von Kossa staining and the amount of calcium was significantly enhanced on the gelatin‐incorporated nanofibers. These results suggest that the chemical composition of the underlying scaffolds play a key role in regulating the osteogenic differentiation of hMSCs.

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Semi‐Covalent Surface Molecular Imprinting of Polymers by One‐Stage Mini‐emulsion Polymerization: Glucopyranoside as a Model Analyte
Authors: Curcio Pasquale , Zandanel Christelle , Wagner Alain , Mioskowski Charles , Baati Rachid
Published: May 2009

This paper describes a new type of surface imprinting technique that combines the advantages of both the semi‐covalent approach and one‐stage miniemulsion polymerization. This process has been successfully applied for the preparation of glucose surface‐imprinted nanoparticles. The selective artificial receptors for glucopyranoside were fully characterized by IR, TEM and BET analyses, and their molecular recognition abilities by binding experiments carried out in batch processes. The molecular affinity and selectivity of the glucose molecularly imprinted polymers were accurately quantified. These characteristics are essential for verification of the efficiency of the developed surface imprinting process. The imprinting effect was clearly demonstrated using the batch rebinding method. We have found that the glucose imprinted polymers produced using the optimized one‐stage mini‐emulsion exhibited quite fast kinetics of binding and equilibration with glucopyranoside templates, compared to polymers prepared by bulk polymerization technique, as well as extremely low levels of unspecific bindings. We also demonstrated that glucose molecular imprinted polymer (MIP) exhibited very good selectivity for its original template compared to other glycopyranoside derivatives, such as galactose. Finally, the extraction of the binding properties from isotherms of binding by fitting to the bi‐Langmuir and Freundlich models allowed the determination of the affinity constant distribution of the binding sites. This imprinting protocol allowed the determination of an affinity constant (KD), involving exclusively H‐bonding interactions, for the glucose MIP (P2C) with the best template 1, in CH3CN as the solvent system.

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Thermoplastic Ternary Hybrids of Polyurethane, Hindered Phenol and Hindered Amine with Selective Two‐Phase Dispersion
Authors: Zhao Xiu‐Ying , Lu Yong‐Lai , Xiao Da‐Ling , Wu Si‐Zhu , Zhang Li‐Qun
Published: May 2009

A novel ternary hybrid of thermoplastic polyurethane/hindered phenol/hindered amine was designed and prepared. Selected hindered phenols and hindered amines were settled down, respectively, in the soft and hard phases of TPU with molecular‐level dispersion. As a result, the ternary hybrid showed a prominent enhancement in the tan δ peak value and distinct broadening of the glass transition region, due to the formation of strong interactions (hydrogen bonding) between segment and small polar molecules occurred in each phase of TPU, which demonstrated the promising future as high‐performance damping material of this ternary hybrid.

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Effect of Melt and Mold Temperatures on the Solidification Behavior of HDPE during Gas‐Assisted Injection Molding: An Enthalpy Transformation Approach
Authors: Yang Bin , Fu Xiao‐Rong , Yang Wei , Liang Shui‐Po , Sun Nan , Hu Sheng , Yang Ming‐Bo
Published: May 2009

The influence of melt and mold temperature on the solidification behavior of HDPE during the GAIM process is studied using a transient‐heat‐transfer model of the enthalpy transformation approach. An in situ measurement of temperature decay in the mold cavity was carried out to verify the simulated results experimentally, and reasonable agreement was observed. The comparison of the HDPE solidification behavior under various cooling conditions reveals that the rapid cooling rate (due to thin wall‐thickness) is the main reason for the shortening of molding cycles, and that the mold temperature shows greater influence on the controlling of cooling rates than melt temperature during GAIM process.

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A Novel Approach for Incorporation of Mono‐Functional Bioactive Phenols into Polyanhydrides
Authors: Prudencio Almudena , Carbone Ashley L. , Griffin Jeremy , Uhrich Kathryn E.
Published: May 2009

Antiseptics based on phenol and phenolic derivatives were chemically incorporated into polyanhydrides as pendant groups via ester linkages. Polyanhydrides with antiseptic loadings of 46–58 wt.‐% were obtained with molecular weights ranging from 9 400–23 000. In general, polymers with the bulkier antiseptics were more difficult to polymerize and yielded lower molecular weights. All polyanhydrides were amorphous with glass transition temperatures ranging from 27–58 °C. Polymers were deemed noncytotoxic after culturing L929 mouse fibroblast cells in media containing the polymers at two concentrations (0.10 and 0.01 mg · mL−1) over three days. In summary, mono‐functional bioactives can be chemically incorporated into noncytotoxic polyanhydrides.

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The dual role of thymidine phosphorylase in cancer development and chemotherapy
Authors: Bronckaers Annelies , Gago Federico , Balzarini Jan , Liekens Sandra
Published: May 2009

Thymidine phosphorylase (TP), also known as “platelet‐derived endothelial cell growth factor” (PD‐ECGF), is an enzyme, which is upregulated in a wide variety of solid tumors including breast and colorectal cancers. TP promotes tumor growth and metastasis by preventing apoptosis and inducing angiogenesis. Elevated levels of TP are associated with tumor aggressiveness and poor prognosis. Therefore, TP inhibitors are synthesized in an attempt to prevent tumor angiogenesis and metastasis. TP is also indispensable for the activation of the extensively used 5‐fluorouracil prodrug capecitabine, which is clinically used for the treatment of colon and breast cancer. Clinical trials that combine capecitabine with TP‐inducing therapies (such as taxanes or radiotherapy) suggest that increasing TP expression is an adequate strategy to enhance the antitumoral efficacy of capecitabine. Thus, TP plays a dual role in cancer development and therapy: on the one hand, TP inhibitors can abrogate the tumorigenic and metastatic properties of TP; on the other, TP activity is necessary for the activation of several chemotherapeutic drugs. This duality illustrates the complexity of the role of TP in tumor progression and in the clinical response to fluoropyrimidine‐based chemotherapy. © 2009 Wiley Periodicals, Inc. Med Res Rev, 29, No. 6, 903–953, 2009
Development of oligomeric prion‐protein aggregates in a mouse model of prion disease
Authors: Sasaki Kensuke , Minaki Haruhiko , Iwaki Toru
Published: May 2009

In prion diseases the normal cellular isoform of prion protein (PrP), denoted PrPC, is converted into an abnormal, pathogenic isoform of PrP (PrPSc). Diagnostic tools for prion diseases are conventionally based on the detection of protease‐resistant PrP (PrPres) after proteinase K digestion. However, recent studies have revealed that protease‐sensitive abnormal PrP (sPrPSc) also exists in significant amounts in brains suffering from prion diseases. Here, we designed a simplified size‐exclusion gel chromatography assay, using disposable spin columns to examine PrP aggregates in the course of the disease, without proteinase K digestion. Brain homogenates of NZW mice, inoculated intracranially with Fukuoka‐1 strain, and which died at around 120 days post‐inoculation, were assayed by this gel‐fractionation method and eluted PrP molecules in each fraction were detected by western blot analysis. Oligomeric PrP molecules were well separated from monomers, as predicted. A conventional protease‐digestion assay was also performed to detect PrPres and revealed that the ratio of PrPres to total PrP increased drastically from 105 days. However, the increase of PrP oligomers became significant from 90 days. These PrP oligomers in the early disease stage would, therefore, be sPrPSc molecules that might affect the disease pathology, such as spongiform change and abnormal PrP deposition. We also observed that the resistance of PrP oligomers to proteinase K and insolubility in phosphotungstic acid precipitation increased with disease progression, which suggests that PrP oligomers are not clearly distinguished from cellular PrP or PrPres but may overlap in a continuous spectrum. Our study casts light on the ambiguity of the definition of PrPSc and indicates that the abnormality of PrP molecules should be determined from various perspectives, more than protease resistance. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Small molecule inhibitors in children with malignant gliomas
Authors: Herrington Betty , Kieran Mark W.
Published: May 2009

Pediatric high grade gliomas (HGG) remain difficult to cure despite recent advances in imaging, neurosurgery, and radiation. Current treatment modalities have demonstrated only modest survival benefit. Research utilizing molecular biologic techniques reveals that the phenotype of HGG is complex and results from dysregulation of numerous inter‐related cellular pathways. Knowledge of potential molecular targets along dysregulated pathways has led to the development of novel and highly specific targeted therapies, which include small molecule inhibitors. This article will review small molecule inhibition of cellular pathways involved in gliomagenesis, challenges to small molecule therapy, and future directions in the use of this therapy. Pediatr Blood Cancer 2009;53:312–317. © 2009 Wiley‐Liss, Inc.
Quality outcomes for a diabetes service
Authors: Sharp PS , Woodman S , Heron W
Published: May 2009

Current NHS policy is to move services for chronic disease out of the hospital sector into the community, with services managed by a variety of health care professionals. There are often no clinical outcome measures specified for such clinics, and we therefore describe results for one such service run by a consultant, a dietitian and a specialist nurse.

The clinic is hosted by an urban GP practice, and reviews patients with a view to problem solving, management planning and discharge.

During a representative period, between 1 April 2007 and 31 March 2008, 144 patients were seen in 285 visits with a new:follow‐up ratio of 1:0.98. The non‐attendance rate runs between 15 and 20%. In a 21‐month period, 213 patients were referred with conditions requiring improvement in diabetes control. Baseline HbA1c was 10.0(0.14)% (mean [SEM]), and had fallen to 8.8(0.12)% at the time of discharge (p<0.01). Fifty‐three of these subjects were judged to need insulin. In this group, the HbA1c fell from 10.64(0.3)% to 8.6(0.2)% (p<0.01). In the remaining 160 individuals who needed reinforcement of advice, tablet or insulin titration, the HbA1c fell from 9.8(0.15)% to 8.8(0.14)% (p<0.01).

The data here provide quality markers for a community diabetes clinic. Further figures from other services are required to provide commissioners with realistic quality markers against which services could be compared. Copyright © 2009 John Wiley & Sons.
Supportive care needs in patients with lung cancer
Authors: Sanders Sharon L. , Bantum Erin O. , Owen Jason E. , Thornton Andrea A. , Stanton Annette L.
Published: May 2009

Introduction: The goal of this study was to characterize the prevalence and intensity of supportive care needs and interest in specific supportive care services among individuals with lung cancer.

Method: Participants (n=109) were recruited from two medical centers in Southern California to complete questionnaires on physical and psychological functioning following diagnosis of lung cancer.

Results: Participants reported the greatest need in the physical and daily living domain, followed by psychological needs, health system and informational needs, and patient care support needs. The most common unmet need was a lack of energy and tiredness (75%). Higher levels of supportive care needs were associated with worse physical functioning (β=−0.30, p<0.001), greater symptom bother (β=0.25, p=0.008), lower satisfaction with health care (β=−0.24, p=0.002), and higher levels of intrusive thoughts about cancer (β=0.40, p<0.001). The sample was most interested in receiving additional information about their disease and treatment (61.0%), exercise‐related information and support (54.3%), and assistance dealing with fatigue (46.7%). Over 91% expressed interest in at least one specific supportive care service, and 51.4% were interested in one or more psychological services.

Conclusion and implications for cancer survivors: Our findings suggest that lung cancer survivors have many unmet needs. Patients who report higher physical distress and intrusive stress symptoms, or lower satisfaction with their health care, may experience the highest level of supportive care need and intervention. Copyright © 2009 John Wiley & Sons, Ltd.
Developmental differences in the contractile response of isolated ovine tracheal smooth muscle cells
Authors: Laudadio Rachel E. , Wolfson Marla R. , Shaffer Thomas H. , Driska Steven P.
Published: May 2009

Previous studies have shown developmental differences in smooth muscle tone of the airways. Differences in airway mechanics may be based upon cellular differences between animals of different ages. We developed a method [Driska et al. J Appl Physiol 86(1): 427–35, 1999] for isolating ovine tracheal smooth muscle cells and for measuring shortening velocity. This technique was used to study the change in contractile response of the airway smooth muscle (ASM) cell during development. Here we report differences between preterm (PT) (110–124 or 125–140 days post‐conception), newborn (NB) (3–7 days postnatal) and adult (9–36 months) cells. These cells were compared with respect to morphometry, shortening velocity, and percent shortening. The neonatal cells were shorter and narrower than the adult cells. Maximum shortening velocity was faster for adult (45.1 µm/sec) than for neonatal cells (range 11.1–25.1 µm/sec). When velocity was normalized to the cell length, there was no difference between the adult and PT cells, but there was a significant difference between the NB (0.30 sec−1) and adult (0.54 sec−1) cells. The percent shortening did not show any significant difference with age. Within the neonatal groups, there were no significant differences in morphometry, shortening or velocity. To facilitate comparison between ASM tissues of different sizes with different sized cells, we also expressed percent shortening and velocities relative to a hypothetical 1 mm segment of tissue. Represented this way, the amount of shortening for all age groups was the same, but the predicted maximum velocity of the hypothetical PT tissue (125–140 days) was significantly greater than for NB. Pediatr Pulmonol. 2009; 44:602–612. © 2009 Wiley‐Liss, Inc.
Individual and cumulative effect of prostate cancer risk‐associated variants on clinicopathologic variables in 5,895 prostate cancer patients
Authors: Kader A. Karim , Sun Jielin , Isaacs Sarah D. , Wiley Kathleen E. , Yan Guifang , Kim Seong‐Tae , Fedor Helen , DeMarzo Angelo M. , Epstein Jonathan I. , Walsh Patrick C. , Partin Alan W. , Trock Bruce , Zheng S. Lilly , Xu Jianfeng , Isaacs William
Published: May 2009

BACKGROUND

More than a dozen single nucleotide polymorphisms (SNPs) have been associated with prostate cancer (PCa) risk from genome‐wide association studies (GWAS). Their association with PCa aggressiveness and clinicopathologic variables is inconclusive.

METHODS

Twenty PCa risk SNPs implicated in GWAS and fine mapping studies were evaluated in 5,895 PCa cases treated by radical prostatectomy at Johns Hopkins Hospital, where each tumor was uniformly graded and staged using the same protocol.

RESULTS

For 18 of the 20 SNPs examined, no statistically significant differences (P > 0.05) were observed in risk allele frequencies between patients with more aggressive (Gleason scores ≥4 + 3, or stage ≥T3b, or N+) or less aggressive disease (Gleason scores ≤3 + 4, and stage ≤T2, and N0). For the two SNPs that had significant differences between more and less aggressive disease rs2735839 in KLK3 (P = 8.4 × 10−7) and rs10993994 in MSMB (P = 0.046), the alleles that are associated with increased risk for PCa were more frequent in patients with less aggressive disease. Since these SNPs are known to be associated with PSA levels in men without PCa diagnoses, these latter associations may reflect the enrichment of low grade, low stage cases diagnosed by contemporary disease screening with PSA.

CONCLUSIONS

The vast majority of PCa risk‐associated SNPs are not associated with aggressiveness and clinicopathologic variables of PCa. Correspondingly, they have minimal utility in predicting the risk for developing more or less aggressive forms of PCa. Prostate 69:1195–1205, 2009. © 2009 Wiley‐Liss, Inc.
Detection of prostate specific transcripts in the peripheral blood during brachytherapy predicts postoperative PSA kinetics
Authors: Mabjeesh Nicola J. , Amir Sharon , Stenger Amira , Chen Juza , Matzkin Haim
Published: May 2009

BACKGROUND

We evaluated whether detection of prostate‐specific antigen (PSA) and human kallikrein 2 (hK2) transcripts in the peripheral blood during brachytherapy could predict biochemical outcome.

METHODS

Eighty‐one patients who underwent 125Iodine‐based brachytherapy for localized prostate cancer (Gleason score <8, PSA <20 ng/ml, stage <T3), participated in the study. Brachytherapy was given to 35 patients as monotherapy, to 36 in combination with androgen deprivation therapy (ADT), and to 10 in combination with external beam radiation and ADT. Blood samples from 80 patients were available for analysis. Nested RT‐PCR means was used to detect mRNA expression of PSA and hK2 in the peripheral blood. Their expression was analyzed before, during and 1 month after brachytherapy. Patients' biochemical outcome (blood PSA levels) during 3 years of follow‐up was correlated with the PCR results.

RESULTS

The incidence of PSA and hK2 mRNA expression in the peripheral blood was significantly higher during than before or after the procedure. Patients with concurrent positive PSA and hK2 PCR results during brachytherapy had higher postoperative blood PSA values and a slower decline rate of PSA compared with patients with negative PSA and hK2 PCR results. No correlations were found between pre‐ and postbrachytherapy PCR results and biochemical outcome. ADT was the only significant factor that affected PSA and hK2 mRNA expression during brachytherapy.

CONCLUSIONS

Our short‐term results suggest that detection of PSA and hK2 transcripts in the peripheral blood of prostate cancer patients during brachytherapy could serve as a predictor of biochemical outcome. Prostate 69:1235–1244, 2009. © 2009 Wiley‐Liss, Inc.
Assessment of global and local model quality in CASP8 using Pcons and ProQ
Authors: Larsson Per , Skwark Marcin J. , Wallner Björn , Elofsson Arne
Published: May 2009

Model Quality Assessment Programs (MQAPs) are programs developed to rank protein models. These methods can be trained to predict the overall global quality of a model or what local regions in a model that are likely to be incorrect. In CASP8, we participated with two predictors that predict both global and local quality using either consensus information, Pcons, or purely structural information, ProQ. Consistently with results in previous CASPs, the best performance in CASP8 was obtained using the Pcons method. Furthermore, the results show that the modification introduced into Pcons for CASP8 improved the predictions against GDT_TS and now a correlation coefficient above 0.9 is achieved, whereas the correlation for ProQ is about 0.7. The correlation is better for the easier than for the harder targets, but it is not below 0.5 for a single target and below 0.7 only for three targets. The correlation coefficient for the best local quality MQAP is 0.68 showing that there is still clear room for improvement within this area. We also detect that Pcons still is not always able to identify the best model. However, we show that using a linear combination of Pcons and ProQ it is possible to select models that are better than the models from the best single server. In particular, the average quality over the hard targets increases by about 6% compared with using Pcons alone. Proteins 2009. © 2009 Wiley‐Liss, Inc.