bluuebunny/crossref_metadata_2025 huggingface dataset:
Precise integration methods based on Lagrange piecewise interpolation polynomials
Authors: Wang Meng‐Fu , Au F. T. K.
Published: August 2008

This paper introduces two new types of precise integration methods for dynamic response analysis of structures, namely, the integral formula method and the homogenized initial system method. The applied loading vectors in the two algorithms are simulated by the Lagrange piecewise interpolation polynomials based on the zeros of the first Chebyshev polynomial. Developed on the basis of the integral formula and the Lagrange piecewise interpolation polynomial and combined with the recurrence relationship of some key parameters in the integral computation suggested in this paper with the solving process of linear algebraic equations, the integral formula method has been set up. On the basis of the Lagrange piecewise interpolation polynomial, and transforming the non‐homogenous initial system into the homogeneous dynamic system, the homogenized initial system method without dimensional expanding is presented; this homogenized initial system method avoids the matrix inversion operation and is a general homogenized high‐precision direct integration scheme. The accuracy of the presented time integration schemes is studied and is compared with those of other commonly used schemes; the presented time integration schemes have arbitrary order of accuracy, wider application and are less time consuming. Two numerical examples are also presented to demonstrate the applicability of these new methods. Copyright © 2008 John Wiley & Sons, Ltd.
A class of multiobjective control problems
Authors: de Oliveira V. A. , Silva G. N. , Rojas‐Medar M. A.
Published: August 2008

We introduce the class of MP‐pseudoinvex multiobjective optimal control problems. We show that the concept of MP‐pseudoinvexity is a sufficient condition of optimality and, further, that problems such that every control process satisfying Pontryagin's maximum principle is an optimal process are necessarily MP‐pseudoinvex problems. Moreover, a sub‐class of the MP‐pseudoinvex problems, which we call MP‐invex multiobjective optimal control problems, is defined. We prove that the set of optimal solutions of MP‐invex multiobjective problems coincides with the set of optimal solutions of a related scalar problem. Copyright © 2008 John Wiley & Sons, Ltd.
ESR1 amplification in endometrial carcinomas: hope or hyperbole?
Authors: Tan DSP , Lambros MBK , Marchiò C , Reis‐Filho JS
Published: August 2008

The ESR1 gene maps 6q25 and encodes for oestrogen receptor alpha, which has been shown to play a pivotal role in the development of breast and endometrial cancer. It has recently been reported that oestrogen receptor alpha expression may be driven in some cases by ESR1 gene amplification and that this phenomenon may be an early event in breast and endometrial carcinogenesis. Although copy number gains of 6q have been reported by several groups, their prevalence, association with oestrogen receptor alpha expression, and clinical implications have been a matter of controversy. Here we discuss the key issues regarding the methods employed in the identification of ESR1 amplification, and briefly review the current literature and recent controversies on the subject of ESR1 amplification in endometrial and breast cancers. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
S‐phase kinase protein 2 is an attractive therapeutic target in a subset of diffuse large B‐cell lymphoma
Authors: Uddin S , Hussain A , Ahmed M , Belgaumi A , Al‐Dayel F , Ajarim D , Bavi P , Al‐Kuraya KS
Published: August 2008

S‐phase kinase protein 2 (SKP2), an F‐box protein, targets cell‐cycle regulators including cycle‐dependent kinase inhibitor p27KiP1 via ubiquitin‐mediated degradation. SKP2 is frequently overexpressed in a variety of cancer cells and has been implicated in oncogenesis; however, its role in diffuse large B‐cell lymphoma (DLBCL) has not been elucidated. Therefore, we investigated the role of SKP2 and its ubiquitin‐proteasome pathway in a large series (301) of DLBCL patient samples and a panel of DLBCL cell lines. Using immunohistochemistry, SKP2 was detected in 41.6% of DLBCL tumours and was inversely associated with p27Kip1 protein level. The DLBCL subset with high SKP2 and low p27Kip1 showed a strong correlation with the proliferating index marker Ki‐67 (p < 0.0001) and also with the germinal centre phenotype (p = 0.0147). Treatment of DLBCL cell lines with bortezomib or expression of SKP2‐specific siRNA causes down‐regulation of SKP2 and accumulation of p27Kip1, leading to suppression of growth by inducing apoptosis. Furthermore, treatment of DLBCL cells with bortezomib causes apoptosis via involving the mitochondrial pathway and activation of caspases. Finally, treatment of DLBCL cells with bortezomib down‐regulated the expression of XIAP, cIAP1, and survivin. Altogether, these results suggest that SKP2 and the ubiquitin‐proteasome pathway may be a potential target for therapeutic intervention in DLBCL. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Protracted haemangioblastic proliferation and differentiation in von Hippel–Lindau disease
Authors: Shively SB , Beltaifa S , Gehrs B , Duong H , Smith J , Edwards NA , Lonser RR , Raffeld M , Vortmeyer AO
Published: August 2008

Von Hippel–Lindau (VHL) disease is caused by germline mutation of the VHL tumour suppressor gene. Patients frequently develop multiple nervous system tumours, denominated haemangioblastomas. Analysis of affected autopsy tissues suggests that tumourigenesis propagates from developmentally arrested, embryonic cells and progresses with consistent architectural, cytological, and molecular sequences similar to haemangioblastic formation and differentiation in the embryo. In this study, we analysed 156 nervous system tumours, 139 of which had been surgically resected from 83 VHL patients. We demonstrate that large tumours consistently contain epithelioid components characteristic of haemangioblastic differentiation in comparison to small tumours that solely display a poorly differentiated, mesenchymal structure. We further show exclusive activation of HIF2α in both small mesenchymal tumours and the mesenchymal component of large tumours, whereas activation of HIF1α is associated with epithelioid structure. We also show that the MIB1 proliferative index is variably increased in the epithelioid component of large tumours, with extramedullary haematopoiesis foci within the epithelioid component at 100%. These data provide compelling evidence that nervous system tumourigenesis in VHL disease represents a protracted process of haemangioblastic proliferation and differentiation that parallels haemangioblastic formation and differentiation in the embryo. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Clinical and biological significance of CXCL12 and CXCR4 expression in adult testes and germ cell tumours of adults and adolescents
Authors: Gilbert DC , Chandler I , McIntyre A , Goddard NC , Gabe R , Huddart RA , Shipley J
Published: August 2008

Interaction between the chemokine CXCL12 (SDF1) and the G‐protein coupled receptor CXCR4 is responsible for the maintenance of adult stem cell niches and is known to play an important role in utero in the migration of primordial germ cells. We demonstrate expression of CXCL12 by Sertoli cells and confirm CXCR4 expression by the germ cell population of the adult human testes. CXCR4 is also known to mediate organ‐specific patterns of metastases in a range of common cancers. We identify consistent expression of CXCR4 mRNA and protein in testicular germ cell tumours (TGCT) that accounts for their patterns of relapse in sites of known CXCL12 expression. Extragonadal primary germ cell tumours express CXCR4 and their sites of occurrence are coincident with areas of known CXCL12 expression in utero. We show that CXCL12 stimulates the invasive migration of a TGCT cell line in vitro in a CXCR4‐dependent fashion and activates ERK. Furthermore, we demonstrate that expression of CXCL12 in stage I non‐seminomas is significantly associated with organ‐confined disease post‐orchidectomy and reduced risk of relapse (p = 0.003). This may be through the loss of CXCL12 gradients that might otherwise attract cells away from the primary tumour. We propose CXCL12 expression as a potential predictor of subsequent relapse that could lead to avoiding unnecessary treatment and associated late toxicities. Our observations support a role for CXCL12/CXCR4 in the adult germ cell population and demonstrate pathological function in germ cell tumour development and metastasis that may have clinical utility. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
A new crosslinked protein fiber from gliadin and the effect of crosslinking parameters on its mechanical properties and water stability
Authors: Li Ying , Reddy Narendra , Yang Yiqi
Published: August 2008

BACKGROUND: Although several cereal proteins have been used to develop fibers and films, it has not been possible to obtain protein materials with good mechanical properties and water stability, even after crosslinking. Previously, high concentrations of glutaraldehyde were used to improve the mechanical properties of protein fibers but the effect of crosslinking conditions on the properties of the crosslinked materials has not been studied in detail.

RESULTS: Low concentrations of glutaraldehyde can be used to improve the mechanical properties and water stability of gliadin fibers. Quantitative relationships that can predict the breaking tenacity of the fibers at various crosslinking conditions are developed. Glutaraldehyde crosslinking is more resistant to hydrolysis in neutral pH than under acidic conditions in terms of increasing and retaining the breaking tenacity. The crosslinked fibers show improved resistance to hydrolysis over poly(lactic acid) fibers in aqueous dispersions at pH = 4 and 7 at 50 and 90 °C, respectively.

CONCLUSIONS: This study shows that low concentrations of glutaraldehyde can impart excellent mechanical properties to gliadin fibers. The quantitative relationships developed can be used to select the crosslinking conditions such low glutaraldehyde concentration and high temperature or vice versa to obtain the desired improvement in mechanical properties or water stability. Copyright © 2008 Society of Chemical Industry
Fabrication of protein‐doped PLA composite nanofibrous scaffolds for tissue engineering
Authors: Yuan Jiang , Shen Jian , Kang Inn‐Kyu
Published: August 2008

BACKGROUND: Electrospinning is known as a novel fabrication method to form nanofibrous scaffolds for tissue‐engineering application. Previously, many natural biopolymers of protein have been electrospun. However, keratin has not attracted enough attention. In this study, keratin and gelatin were co‐electrospun with polylactide (PLA), respectively.

RESULTS: The resulting nanofibers were characterized by a field emission scanning electron microscope (FE‐SEM), an attenuated total reflection‐Fourier transform infrared spectroscopy (ATR‐FTIR), and an electron spectroscopy for chemical analysis (ESCA). The biodegradation of mats in the presence of trypsin solution was studied. Cell attachment experiments showed that NIH 3T3 cells adhered more and spread better onto the PLA/keratin and PLA/gelatin nanofibrous mats than that onto the blank PLA mats. MTT and BrdU assay showed that PLA/keratin and PLA/gelatin nanofibrous mats could both accelerate the viability and proliferation of fibroblast cells as compared to PLA nanofibrous mats.

CONCLUSION: The present study suggests that the introduction of gelatin and keratin can both improve cell‐material interaction, especially, the former is more effective. Copyright © 2008 Society of Chemical Industry
Effect of electric potential and coulombic interactions on electrospinning nanofiber distribution
Authors: Zhang Jian‐Feng , Yang Dong‐Zhi , Nie Jun
Published: August 2008

BACKGROUND: Electrospinning is a versatile method to process solutions or melts into micro‐ or nanofibers. Several mathematic models for electrospinning have been established, focused mostly on the fiber formation process, but seldom on the distribution of collected fibers by considering the electric field effect.

RESULTS: A method based on electric potential and coulombic interactions was developed to simulate the distribution of electrospun fibers. Two different types of electric field were investigated; and the process was interpreted by schematic diagrams and physical equations. In this case, the simulation analysis based on idealized models is convenient to understand the effect of the distorted electric field induced by different types of collectors.

CONCLUSION: The effects of electric potential and Coulombic interactions are the decisive factors in the collect process. The mathematic model can indeed predict the distribution of electrospun fibers. Copyright © 2008 Society of Chemical Industry
A “plug and play” polymer through biocomplementary hydrogen bonding
Authors: Cheng Chih‐Chia , Huang Chih‐Feng , Yen Ying‐Chieh , Chang Feng‐Chih
Published: August 2008

This article describes a DNA‐like polymer that exhibits the ability to self‐assemble through hydrogen bonding. We synthesized poly[1‐(4‐vinylbenzyl)thymine] (PVBT) and 9‐hexadecyladenine (A‐C16) through an atom transfer radical polymerization (ATRP) and alkylation, respectively. Biocomplementary PVBT/A‐C16 hierarchical supramolecular complexes formed in dilute DMSO solution through nucleobase recognition, that is, hydrogen bonding interactions between the thymine (T) groups of PVBT and the adenine (A) group of A‐C16; evidence for this molecular recognition was also gained from dynamic light scattering studies. 1H NMR titration studies in CDCl3 showed that T–A complexes formed rapidly on the NMR time scale with high association constants (up to 534 M−1). Moreover, FTIR spectroscopic, differential scanning calorimetry, wide‐angle X‐ray diffraction, and small‐angle X‐ray scattering analyses provided further details into the nature of the self‐assembly of these systems. In the bulk state, these complexes self‐assemble into well‐ordered lamellar structures; the changing d‐spacing distance (ranging from 4.98 to 2.32 nm) at different A‐C16 loadings reveals that the molecular structures of the PVBT/A‐C16 complexes are readily tailored. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6416–6424, 2008
Synthesis and characterization of amphiphilic block copolymer of polyphosphoester and poly(L‐lactic acid)
Authors: Yang Xian‐Zhu , Wang Yu‐Cai , Tang Ling‐Yan , Xia Hai , Wang Jun
Published: August 2008

Aliphatic polyesters and polyphosphoesters (PPEs) have received much interest in medical applications due to their favorable biocompatibility and biodegradability. In this work, novel amphiphilic triblock copolymers of PPE and poly(L‐lactic acid) (PLLA) with various compositions were synthesized and characterized. The blocky structure was confirmed by GPC analyses. These triblock copolymers formed micelles composed of hydrophobic PLLA core and hydrophilic PPE shell in aqueous solution. Critical micellization concentrations of these triblock copolymers were related to the polymer compositions. Incubation of micelles at neutral pH followed by GPC analyses revealed that these polymer micelles were hydrolysized and resulted in decreased molecular weights and small oligomers, whereas its degradation in basic and acid mediums was accelerated. MTT assay also demonstrated the biocompatibility against HEK293 cells. These biodegradable polymers are potential as drug carriers for biomedical application. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6425–6434, 2008
Enzymatic and chemical hydrolysis of poly(ethylene terephthalate) fabrics
Authors: Brueckner Tina , Eberl Anita , Heumann Sonja , Rabe Maike , Guebitz Georg M.
Published: August 2008

Alkaline and enzymatic hydrolyzes of poly(ethylene terephthalate) fabrics (PET) were mechanistically compared based on released degradation products (HPLC‐UV‐RI) and changes in surface properties [hydrophilicity, cationic dyeing, X‐ray photoelectron spectroscopy (XPS)]. Enzymatic hydrolysis led to an increase in the amount of hydroxyl and carboxyl groups on the surface resulting in an enhanced water absorption and dyeability. Enzymes partially adsorbed to PET fabrics during hydrolysis were completely removed by subsequent extraction according to XPS analysis. In contrast to the enzyme treatment, alkaline hydrolysis did not lead to an increase of hydroxyl and acid groups according to XPS while both treatments caused a substantial increase in hydrophilicity and were more effective on amorphous fibers. Alkaline hydrolysis led to a greater increase in the K/S value after cationic dyeing due to enlarged surface area. Consequently, ESEM‐images demonstrated that alkaline treatment drastically affected the surface morphology of the polymer resulting in crater‐like structures of the fibers, whereas after enzymatic treatment the morphology of the fibers remained unchanged. To reach similar benefits in hydrophilicity, drastically higher amounts of degradation products were released during alkaline hydrolysis as also indicated by >6% weight loss compared to <1% after enzyme treatment. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6435–6443, 2008
Synthesis of various stimuli‐responsive gradient copolymers by living cationic polymerization and their thermally or solvent induced association behavior
Authors: Seno Ken‐Ichi , Tsujimoto Itsuko , Kanaoka Shokyoku , Aoshima Sadahito
Published: August 2008

Stimuli‐responsive gradient copolymers, composed of various monomers, were synthesized by living cationic polymerization in the presence of base. The monomers included thermosensitive 2‐ethoxyethyl vinyl ether (EOVE) and 2‐methoxyethyl vinyl ether (MOVE), hydrophobic isobutyl vinyl ether (IBVE) and 2‐phenoxyethyl vinyl ether (PhOVE), crystalline octadecyl vinyl ether (ODVE), and hydrophilic 2‐hydroxyethyl vinyl ether (HOVE). The synthesis of gradient copolymers was conducted using a semibatch reaction method. Living cationic polymerization of the first monomer was initiated using a conventional syringe technique, followed by an immediate and continuous addition of a second monomer using a syringe pump at regulated feed rates. This simple method permitted precise control of the sequence distribution of gradient copolymers, even for a pair of monomers with very different relative monomer reactivities. The stimuli‐responsive gradient, block and random copolymers exhibited different self‐association behavior. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6444–6454, 2008
Preparation of flexible and transparent polylactic acids films by crystallization manipulation
Authors: Lertworasirikul Amornrat , Arikawa Yuuya , Kaneko Tatsuo , Kida Toshiyuki , Akashi Mitsuru
Published: August 2008

Highly flexible and transparent polylactic acids (PLAs) films were successfully prepared by manipulating their crystallization. The semicrystalline poly(L‐lactic acid) (L) was blended with a noncrystalline poly(DL‐lactic acid) (DL) together with diglycerol tetraacetate (DGTA). Optimal DGTA content to plasticize PLAs was about 17%. Addition of DL hindered the crystallization of the films. Tensile strengths of the films having DL content more than 5% were about 10 MPa while the elongations at break were boosted as DL content increased. Films having L/DL ratio of 50/50 showed elongations at break of 270%. Stretch ability and clarity of films containing 15–50% DL were fair although they were subjected to annealing at 60 °C for 1 h. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6489–6495, 2008
Synthesis and characterization of well‐defined polystyrene and poly(ε‐caprolactone) hetero eight‐shaped copolymers
Authors: Shi Gang‐Yin , Yang Li‐Ping , Pan Cai‐Yuan
Published: August 2008

Well‐defined hetero eight‐shaped copolymers composed of polystyrene (PS) and poly(ε‐caprolactone) (PCL) with controlled molecular weight and narrow molecular weight distribution were successfully synthesized by the combination of ring‐opening polymerization, ATRP, and “click” reaction. The synthetic procedure involves three steps: (1) preparation of a tetrafunctional PS and PCL star copolymer with two PS and two PCL arms using the tetrafunctional initiator bearing two hydroxyl groups and two bromo groups; (2) synthesis of tetrafunctional star copolymer, (α‐acetylene‐PCL)2(ω‐azido‐PS)2, by the transition of terminal hydroxyl and bromo groups to acetylene and azido groups through the reaction with 4‐propargyloxybutanedioyl chloride and NaN3 respectively; (3) intramolecular cyclization reaction to produce the hetero eight‐shaped copolymers using “click” chemistry under high dilution. The 1H NMR, FTIR, and gel permeation chromatography techniques were applied to characterize the chemical structures of the resulted intermediates and the target polymers. Their thermal behavior was investigated by DSC, and their crystallization behaviors of PCL were studied by polarized optical microscopy. The decrease in chain mobility of the eight‐shaped copolymers restricts the crystallization of PCL and the crystallization rate of PCL is slower in comparison with their corresponding star precursors. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6496–6508, 2008
High performance thermosets from a curable Diels–Alder polymer possessing benzoxazine groups in the main chain
Authors: Chou Ching‐I , Liu Ying‐Ling
Published: August 2008

A high‐molecular‐weight polymer (PBz) possessing reactive benzoxazine groups in the main chain was prepared through the Diels–Alder reaction using bis(3‐furfuryl‐3,4‐dihydro‐2H‐1,3‐benzoxazinyl)isopropane (BPA‐FBz) and bismaleimide (BMI) as monomers. The chemical structure of PBz is characterized with FTIR and 1H NMR. The polymer PBz was further thermally reacted with a high performance polymer (PBz‐R) through the ring‐opening addition reaction of benzoxazine groups and the addition reaction of maleimide groups. PBz‐R exhibit a high glass transition temperature of 242 °C, good thermal stability, high flame retardancy, high mechanical strength, and great flexibility. Another crosslinked polymer (PBz‐BR) curing from the mixture of BPA‐FBz and BMI was also prepared. The properties of PBz‐BR are also attractive but, however, not as good as what observed with PBz‐R. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6509–6517, 2008
Gold nanoparticle‐incorporated core and shell crosslinked micelles fabricated from thermoresponsive block copolymer of N‐isopropylacrylamide and a novel primary‐amine containing monomer
Authors: Zhou Yueming , Jiang Kunqiang , Chen Yaqiong , Liu Shiyong
Published: August 2008

A novel primary amine‐containing monomer, 1‐(3′‐aminopropyl)‐4‐acrylamido‐1,2,3‐triazole hydrochloride (APAT), was prepared from N‐propargylacrylamide and 3‐azidopropylamine hydrochloride via copper‐catalyzed Huisgen 1,3‐dipolar cycloaddition (click reaction). Poly(N‐isopropylacrylamide)‐b‐poly(1‐(3′‐aminopropyl)‐4‐acrylamido‐1,2,3‐triazole hydrochloride), PNIPAM‐b‐PAPAT, was then synthesized via consecutive reversible addition‐fragmentation chain transfer polymerizations of N‐isopropylacrylamide and APAT. In aqueous solution, the obtained thermoresponsive double hydrophilic block copolymer dissolves molecularly at room temperature and self‐assembles into micelles with PNIPAM cores and PAPAT shells at elevated temperature. Because of the presence of highly reactive primary amine moieties in PAPAT block, two types of covalently stabilized nanoparticles namely core crosslinked and shell crosslinked micelles with ‘inverted’ core‐shell nanostructures were facilely prepared upon the addition of glutaric dialdehyde at 25 and 50 °C, respectively. In addition, the obtained structure‐fixed micelles were incorporated with gold nanoparticles via in situ reduction of preferentially loaded HAuCl4. High resolution transmission electron microscopy revealed that gold nanoparticles can be selectively loaded into the crosslinked cores or shells, depending on the micelle templates employed. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6518–6531, 2008
Synthesis, properties, and sulfonation of novel dendritic multiblock copoly(ether‐sulfone)
Authors: Matsumura Sumiko , Hlil Antisar R. , Hay Allan S.
Published: August 2008

Multiblock copoly(ether‐sulfone)s (PESs) bearing anchor units for the construction of dendritic blocks were synthesized by two‐step reactions: (1) synthesis of PES block with both phenoxide end‐groups; (2) chain extension and end‐capping of the block by use of excess novel hexafunctional agent, hexakis(4‐(4‐fluorophenylsulfonyl)phenyl)benzene. The optimum average block length (n) and amount (x) of the hexafunctional agent used for the synthesis of high‐molecular‐weight PES without crosslinking were n = 26 and x = 2.6 equiv, respectively. The dendritic blocks in the PES were constructed by the aromatic nucleophilic substitution reaction of the activated aromatic fluoride groups on the anchor units using 4‐tritylbenzenethiol. The clean substitution of the fluoride groups in the PES was confirmed by 1H NMR and 19F NMR. Three sulfonic acid groups were introduced on the pendant phenyl rings of the trityl groups in the PES by the reaction with chlorosulfonic acid. This is the first example of a dendritic PES bearing clusters of sulfonic acid groups only on the dendritic blocks. Cast films of presulfonated dendritic PES were strong and flexible, however, the membranes of sulfonated dendritic PES were brittle so that the conductivity measurements were not performed. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6365–6375, 2008
Miscibility, morphology, and thermal properties of hyperbranched polyborates modified phenolic resins
Authors: Liu Yuhong , Jing Xinli
Published: August 2008

A series of hyperbranched polyborates (HB) terminated with phenol hydroxyl (HBp) and boric acid hydroxyl (HBb) functional groups, respectively, were blended with phenolic resins (PR). The miscibility and specific interaction behaviors of the HB and PR were investigated by differential scanning calorimetry (DSC) and Fourier Transform infrared spectroscopy (FTIR). Cure behaviors and thermal properties of PR containing different content of HB were also studied. In addition, thermogravimetry analysis (TGA) exhibited apparent increase in thermal stability at both the initial stages and residue weight at 800 °C under nitrogen atmosphere, especially, for the HBb10/90 system that has a temperature of 458 °C at 5% mass loss and a residue weight of 75.4%. Moreover, scanning electron microscope (SEM) revealed that the initially homogeneous phase separated into two‐phase structure after the cure process, which offers a route to achieve new properties combinations that are desirable for high performance polymers. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 2012–2021, 2008
Polymer structure‐dependent ion interaction studied by amphiphilic nonionic poly(organophosphazenes)
Authors: Ahn Sungsook , Ahn Sung Won , Song Soo‐Chang
Published: August 2008

The relative effectiveness of anions and cations in altering macromolecular conformation was reported to be independent of the nature of the macromolecule. However, in terms of the degree of changes, macromolecule‐dependent ion action cannot be underestimated. The designed poly(organophosphazenes) have been selected for this study due to its versatility of the substitution with a fixed backbone. To set up the systematic explanation on the ion action related with molecular interactions, ions and polymers are arranged based on the water binding ability. As a characteristic factor specific in the thermothickening system, the temperature at which the viscosity of the polymer solution reaches the maximum (Tmax) has been compared. Anions with strong water binding ability more effectively lower the Tmax of the hydrophobic poly(organophosphazenes). Meanwhile, the Tmax of the cation‐complexed poly(organophosphazenes) are lowered by the sequence of water binding ability of the complexed cations. In both the anion and cation interactions, poly(organophosphazenes) substituted by longer PEG and more hydrophilic amino acid ester, show differentiated result due to different interaction with water when compared with other polymer systems in this study. Ion interaction with poly(organophosphazenes) mediated by water supports interfacial interactions expressed by interaction parameters, which strongly depends on the polymer structure and ion type. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 2022–2034, 2008
Melting behavior of a poly(ether‐block‐amide) copolymer melt‐crystallized under quiescent, isothermal conditions
Authors: Guo Xiaoping
Published: August 2008

Segmented poly(ether‐block‐amide) copolymers are typically known as polyamide‐based thermoplastic elastomers consisting of hard, crystallizable polyamide block and flexible, amorphous polyether block. The melting characteristics of a poly(ether‐block‐amide) copolymer melt‐crystallized under various quiescent, isothermal conditions were calorimetrically investigated using differential scanning calorimetry (DSC). For such crystallized copolymer samples, their crystalline structures under ambient condition and the structural evolutions upon heating from ambient to complete melting were characterized using ambient and variable‐temperature wide‐angle X‐ray diffractometry (WAXD), respectively. It was observed that dependent of specific crystallization conditions, the copolymer samples exhibited one, two, or three melting endotherms. The ambient WAXD results indicated that all melt‐crystallized copolymer samples only exhibited γ‐form crystals associated with the hexagonal habits of the polyamide homopolymer, whereas variable‐temperature WAXD data suggested that upon heating from ambient, a melt‐crystallized copolymer might exhibit so‐called Brill transition before complete melting. Based on various DSC and variable‐temperature WAXD experimental results obtained in this study, the applicability of different melting mechanisms that might be responsible for multiple melting characteristics of various crystallized PEBA copolymer samples were discussed. It was postulated that the low (T
m1) endotherm was primarily because of the disruption of less thermally stable, short‐range ordered structure of amorphous polyamide segments of the copolymer, which was only formed after the completion of primary crystallization via so‐called annealing effects. The intermediate (Tm2) and high (Tm3) endotherms were attributed to the melting of primary crystals within polyamide crystalline microdomains of the copolymer. The appearance of these two melting endotherms might be somehow complicated by thermally induced Brill transition. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 2035–2046, 2008
Tunable morphologies of rhenium complex‐containing polystyrene‐block‐poly(2‐vinylpyridine) aggregates
Authors: Xu Peng , Ji Xin , Abetz Volker , Jiang Shimei , Shen Jiacong
Published: August 2008

Polystyrene‐block‐poly(2‐vinylpyridine) (PS‐b‐P2VP) diblock copolymer was functionalized with luminescent chlorotricarbonyl rhenium (I) phenanthroline complex in the presence of silver perchlorate. The copolymer‐metal complex showed high sensitivity to the solvent system. Different morphologies and dimensions of the rhenium complex within nanosized micelles were controlled by changing the solvent systems. Core‐embedded rhenium complex within micelles appear by adding methanol, a poor solvent for the copolymer‐metal complex, to the solution of common solvent tetrahydrofuran (THF); the number of the core‐embedded rhenium complex and the scale of the micelles are strongly related to the addition of methanol. Moreover, a novel morphology of corona‐embedded rhenium complex micelles was prepared by dropping the original THF solution of copolymer‐metal complex into water at a low pH value. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 2047–2053, 2008
Pleural effusion due to intra‐abdominal extravasation of parenteral nutrition
Authors: Been Jasper V. , Degraeuwe Pieter L.J.
Published: August 2008

An 8‐week‐old preterm boy experienced respiratory deterioration due to unilateral pleural effusion. Intra‐abdominal extravasation of parenteral fluid with leakage into the pleural cavity was suspected based on biochemical analysis of the effluent. Perforation of the central venous catheter in the peritoneal cavity was subsequently confirmed by contrast roentgenography. As in peritoneal dialysis and hepatic hydrothorax, pleuroperitoneal communication needs to be considered in patients exhibiting pleural effusion with a central venous line below the diaphragm. Pediatr Pulmonol. 2008; 43:1033–1035. © 2008 Wiley‐Liss, Inc.
Bringing diagnostic technologies to the clinical laboratory: Rigor, regulation, and reality
Authors: Whiteley Gordon
Published: August 2008

With the numerous reports of new technologies and biomarkers reported in the literature, it may be surprising that there are not an equal number of new products available to the clinical diagnostic laboratory. Powerful potential tools such as protein microarrays and MS patterns have been extensively published yet commercialization and acceptance of these technologies has yet to happen. The reasons for this are a combination of industry risk avoidance, academic focus on discovery, and a lack of appreciation for the high standards and regulation that surrounds the clinical diagnostic laboratory. The development and validation of a new technology or biomarker ensures that a test is reproducible, controllable, and has a defined accuracy and clinical predictive result but this information is only obtained through somewhat mundane but necessary experimental work. The use of design of experiment principles helps to define material parameters to ensure performance. The organization and documentation of this work through a quality system is both mandated and practical. All of this must be done before a test can reach the market with the safety and effectiveness review of regulatory agencies.
Analysis of biofluids for biomarker research
Authors: Xu Xia , Veenstra Timothy D.
Published: August 2008

While many of the developments made in high‐throughput proteomics were originally applied to procaryotic and simple eucaryotic organisms, the analysis of biofluids became increasingly important as the prospect of using proteomics to discover novel biomarkers became realized. Biofluids have represented a unique challenge to proteomics as they are often present only in small amounts and, particularly in the cases of serum and plasma, can have protein concentration ranges that differ by ten orders of magnitude. While the discovery of authentic, clinically useful biomarkers in the proteomics era has been lacking, there have been a number of significant developments in the ability to more comprehensively characterize biofluid proteomes. The rapid pace of these developments suggest that the eventual discovery of clinically validate biomarkers using proteomic technologies still has a bright future.
A well‐based reverse‐phase protein array applicable to extracts from formalin‐fixed paraffin‐embedded tissue
Authors: Chung Joon‐Yong , Lee Seo‐Jin , Kris Ylaya , Braunschweig Till , Traicoff June L. , Hewitt Stephen M.
Published: August 2008

Proteomic analysis of formalin‐fixed paraffin‐embedded (FFPE) tissue offers significant diagnostic utility but is complicated due to the high level of covalently crosslinked proteins arising from formalin fixation. To address these challenges, we developed a reliable protein extraction method for FFPE tissue, based on heat‐induced antigen retrieval within a pressure cooker. The protein extraction yield from archival FFPE tissue section is approximately 90% of that recovered from frozen tissue. This method demonstrates preservation of immunoreactivity and recovery of full‐length proteins by Western blotting. Additionally, we developed a well‐based RP protein array platform utilizing an electrochemiluminescence detection system. Protein samples derived from FFPE tissue by means of laser capture dissection, with as few as 500 shots demonstrate measurable signal differences for different proteins. The lysates coated to the array plate, remain stable over 1 month at room temperature. Theses data suggest that this new protein‐profiling platform coupled with the protein extraction method can be used for molecular profiling analysis in FFPE tissue, and contribute to the validation and development of biomarkers in clinical studies.
Imaging mass spectrometry: Towards clinical diagnostics
Authors: Seeley Erin H. , Caprioli Richard M.
Published: August 2008

Imaging MS (IMS) has emerged as a powerful tool for biomarker discovery. A key advantage of this technique is its ability to probe the proteome directly from a tissue section with preservation of the spatial relationships of the sample and minimal sample preparation. This allows for direct correlation of protein expression with histology. Here, we present the latest developments in imaging MS and their relevance to clinical mass spectral analysis. IMS allows for high throughput analysis of tissue samples and is fully compatible with biostatistical analysis without prior knowledge of protein expression. Several studies are presented of applications in which direct tissue mass spectral analysis has provided insight into clinical questions not readily available by other means. Examples include the determination of lymph node status from investigation of primary breast tumors, prediction of response of breast tumors to chemotherapy, classification and prediction of progression of lung lesions, and exploration of ‘molecular’ margins in invasive disease.
High‐resolution biomarker discovery: Moving from large‐scale proteome profiling to quantitative validation of lead candidates
Authors: Hewel Johannes A. , Emili Andrew
Published: August 2008

Diverse proteomic techniques based on protein MS have been introduced to systematically characterize protein perturbations associated with disease. Progress in clinical proteomics is essential for personalized medicine, wherein treatments will be tailored to individual needs based on patient stratification using noninvasive disease monitoring procedures to reveal the most appropriate therapeutic targets. However, breakthroughs await the successful development and application of a robust proteomic pipeline capable of identifying and rigorously assessing the relevance of multiple candidate proteins as informative diagnostic and prognostic indicators or suitable drug targets involved in a pathological process. While steady progress has been made toward more comprehensive proteome profiling, the emphasis must now shift from in depth screening of reference samples to stringent quantitative validation of selected lead candidates in a broader clinical context. Here, we present an overview of the emerging proteomic strategies for high‐throughput protein detection focused primarily on targeted MS/MS as the basis for biomarker verification in large clinical cohorts. We discuss the conceptual promise and practical pitfalls of these methods in terms of achieving higher dynamic range, higher throughput, and more reliable quantification, highlighting research avenues that merit additional inquiry.
Dose‐dependent growth inhibition in vivo of PC‐3 prostate cancer with a reduction in tumoral growth factors after therapy with GHRH antagonist MZ‐J‐7‐138
Authors: Heinrich Elmar , Schally Andrew V. , Buchholz Stefan , Rick Ferenc G. , Halmos Gabor , Mile Melinda , Groot Kate , Hohla Florian , Zarandi Marta , Varga Jozsef L.
Published: August 2008

Background

Antagonists of growth hormone‐releasing hormone (GHRH) inhibit the growth of various cancers and affect tumoral growth factors.

Methods

We investigated the effect of a new GHRH antagonist MZ‐J‐7‐138 at doses of 1.25, 2.5, 5 and 10 µg/day s.c. on the growth of PC‐3 human androgen independent prostate cancers xenografted s.c. into nude mice. Binding assays were used to investigate GHRH receptors. The levels of IGF‐II and VEGF in tumors were measured by radioimmunoassays.

Results

Treatment with 2.5, 5, and 10 µg/day MZ‐J‐7‐138 caused a significant dose‐dependent growth reduction of PC‐3 tumors. The greatest inhibition of 78% was obtained with 10 µg/day. The suppression of IGF‐II protein levels in tumors was seen at all doses of MZ‐J‐7‐138, but only 10 µg dose induced a significant inhibition. MZ‐J‐7‐138 also reduced VEGF protein levels, the inhibition being significant at doses of 5 and 10 µg. Specific high affinity binding sites for GHRH were found on PC‐3 tumors using 125I‐labeled GHRH antagonist JV‐1‐42. MZ‐J‐7‐138 displaced radiolabeled JV‐1‐42 with an IC50 of 0.32 nM indicating its high affinity to GHRH receptors. Real‐time PCR analyses detected splice variant 1 (SV1) of GHRH receptor (GHRH‐R) as well as pituitary type of GHRH‐R and GHRH ligand.

Conclusion

Our results demonstrate the efficacy of GHRH antagonist MZ‐J‐7‐138 in suppressing growth of PC‐3 prostate cancer at doses lower than previous antagonists. The reduction of levels of growth factors such as VEGF and IGF‐II in tumors by GHRH antagonist was correlated with the suppression of tumor growth. Prostate © 2008 Wiley‐Liss, Inc.
A 3‐D QSAR Study of Catechol‐O‐Methyltransferase Inhibitors Using CoMFA and CoMSIA
Authors: Ai Chunzhi , Wang Yonghua , Li Yan , Li Yanhong , Yang Ling
Published: August 2008

Inhibitors of Catechol‐O‐Methyltransferase (COMT) play an important role in the treatment of Parkinson's Disease (PD). A new Three‐Dimensional Quantitative Structure–Activity Relationship (3‐D QSAR) analysis was performed on 36 previously reported COMT inhibitors employing Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) methodologies to correlate the molecular fields and percent inhibition values and three predictive models were derived. The CoMFA and CoMSIA models with steric and electrostatic field yielded cross‐validatedr$\rm{ _{{\rm{cv}}}^2 }$sof 0.585 and 0.528, respectively whereas the conventionalr$\rm{ _{{\rm{ncv}}}^2 }$swere 0.979 and 0.891, respectively. The CoMSIA model with hydrophobic field exhibited ar$\rm{ _{{\rm{cv}}}^2 }$of 0.544 and ar$\rm{ _{{\rm{ncv}}}^2 }$of 0.930. The individual inspection of 3‐D contours generated from these models helps in understanding the possible region for structural modification of molecules to improve the inhibitory bioactivity. These 3‐D QSAR models are also useful for designing and predicting novel COMT inhibitors.
Incorporation of carbon and nitrogen atoms into proteins measured by protein‐based stable isotope probing (Protein‐SIP)
Authors: Jehmlich Nico , Schmidt Frank , Hartwich Mathias , von Bergen Martin , Richnow Hans‐Hermann , Vogt Carsten
Published: August 2008

The identification of metabolically active microbial key players is fundamental for understanding the structure and functions of contaminant‐degrading communities. The metabolic activity can be analysed by feeding the microbial culture with stable‐isotope‐labelled substrates and subsequently tracing their incorporation into the biomass. In this paper we present a method which is able to detect the incorporation of stable isotopes from the substrate into the proteins of a benzene‐metabolising microorganism. Pseudomonas putida strain ML2 was grown under aerobic conditions with the substrates 12C‐benzene, 13C‐benzene or 15N‐ammonium and 12C‐benzene. Proteins of these cultures were resolved by two‐dimensional gel electrophoresis (2‐DE) and corresponding protein spots were subjected to matrix‐assisted laser ionization/desorption mass spectrometric (MALDI‐MS) analysis. The proteins of the 12C‐sample were identified by peptide mass fingerprinting (PMF) as well as by tandem mass spectrometric (MS/MS) measurements. The 13C‐ or 15N‐content of the peptides from the labelling experiments was determined by MALDI‐MS/MS. The incorporation of heavy isotopes into the proteins from cultures grown on 13C‐benzene and 15N‐ammonium was determined based on the mass differences between labelled and non‐labelled peptides as well as on the isotopic distribution of the y1‐ion of arginine. The method we present here principally allows the unravelling of the carbon and nitrogen flow not only in pure cultures, but also in microbial communities consisting of many microbial species. Copyright © 2008 John Wiley & Sons, Ltd.
Ionization and fragmentation of monochloro‐isomers of 3‐hydroxy‐2‐phenyl‐4(1H)‐quinolinone
Authors: Grepl Martin , Roithová Jana , Hradil Pavel , Lemr Karel
Published: August 2008

Electron ionization (EI), methane chemical ionization (CI), and collision‐induced dissociation (CID) mass spectra of complete series of positional monochloro‐isomers of 3‐hydroxy‐2‐phenyl‐4(1H)‐quinolinone are evaluated and discussed. It is shown that in the CI experiments, in addition to the protonated precursor molecules, odd‐electron molecular ions are formed and this affects the appearance of the CID spectra. The influence of different direct probes and other experimental parameters such as the pressure of the reagent gas, isolation width, or collision energy was studied. EI, CI and CID spectra of the positional isomers show essentially the same fragmentation pathways but comparisons of the relative signal intensities of various product ions reveal some positional effects. Different isomers are also distinguished. The compounds can be divided into two groups using diagnostic ions (chloro substitution of the quinolinone moiety or the phenyl ring) or identified using a created spectral database. It was demonstrated that the reproducibility of the CID spectra is fully satisfactory for isomer identification, and that the created database can be applied for comparison of spectra measured over an extended time period (1 month) or spectra obtained during the direct analysis of a reaction mixture extract. Explanation of the fragmentation of the isomers is supported by exploratory density functional theory (DFT) calculations, e.g. rationalization of the relatively higher importance of the M+.‐H.‐Cl.‐CO fragmentation pathway during EI than during CID, and vice versa for the pathway M+.‐Cl.‐CO. Copyright © 2008 John Wiley & Sons, Ltd.
Stabilization of complex cascade systems using boundedness information in finite time
Authors: Ye Huawen , Gui Weihua , Liu Guo‐Ping
Published: August 2008

In this paper, the stabilization problem of several classes of complex cascade systems is investigated from a new point of view. If the closed‐loop system is proven to have no finite escape time, the boundedness information in finite time, which is obtained from robust stable subsystems or recursive analysis procedures, is then sufficiently employed to deal with crucial nonlinear terms. The proposed method does not rely on complicated Lyapunov functions, and in some cases it can avoid strong growth conditions and complicated small gain analysis. In addition, simple saturated control laws are explicitly constructed in an almost unified way. Copyright © 2008 John Wiley & Sons, Ltd.