bluuebunny/crossref_metadata_2025 huggingface dataset:
Anesthetic effects on regional CBF, BOLD, and the coupling between task‐induced changes in CBF and BOLD: An fMRI study in normal human subjects
Authors: Qiu Maolin , Ramani Ramachandran , Swetye Michael , Rajeevan Nallakkandi , Constable R. Todd
Published: September 2008

Functional MR imaging was performed in sixteen healthy human subjects measuring both regional cerebral blood flow (CBF) and blood oxygen level dependent (BOLD) signal when visual and auditory stimuli were presented to subjects in the presence or absence of anesthesia. During anesthesia, 0.25 mean alveolar concentration (MAC) sevoflurane was administrated. We found that low‐dose sevoflurane decreased the task‐induced changes in both BOLD and CBF. Within the visual and auditory regions of interest inspected, both baseline CBF and the task‐induced changes in CBF decreased significantly during anesthesia. Low‐dose sevoflurane significantly altered the task‐induced CBF‐BOLD coupling; for a unit change of CBF, a larger change in BOLD was observed in the anesthesia condition than in the anesthesia‐free condition. Low‐dose sevoflurane was also found to have significant impact on the spatial nonuniformity of the task‐induced coupling. The alteration of task‐induced CBF‐BOLD coupling by low‐dose sevoflurane introduces ambiguity to the direct interpretation of functional MRI (fMRI) data based on only one of the indirect measures—CBF or BOLD. Our observations also indicate that the manipulation of the brain with an anesthetic agent complicates the model‐based quantitative interpretation of fMRI data, in which the relative task‐induced changes in oxidative metabolism are calculated by means of a calibrated model given the relative changes in the indirect vascular measures, usually CBF and BOLD. Magn Reson Med 60:987–996, 2008. © 2008 Wiley‐Liss, Inc.
Three‐dimensional high‐resolution magnetic resonance spectroscopic imaging for absolute quantification of 31P metabolites in human liver
Authors: Chmelík M. , Schmid A. I. , Gruber S. , Szendroedi J. , Krššák M. , Trattnig S. , Moser E. , Roden M.
Published: September 2008

Liver dysfunction correlates with alterations of intracellular concentrations of 31P metabolites. Localization and absolute quantification should help to trace regional hepatic metabolism. An improved protocol for the absolute quantification of 31P metabolites in vivo in human liver was developed by employing three‐dimensional (3D) k‐space weighted spectroscopic imaging (MRSI) with B1‐insensitive adiabatic excitation. The protocol allowed for high spatial resolution of 17.8 ± 0.22 cm3 in 34 min at 3 T. No pulse adjustment prior to MRSI measurement was necessary due to adiabatic excitation. The protocol geometry was identical for all measurements so that one calibration data set, acquired from phantom replacement measurement, was applied for all quantifications. The protocol was tested in 10 young, healthy volunteers, for whom 57 ± 7 spectra were quantified. Concentrations per liter of liver volume (reproducibilities) were 2.24 ± 0.10 mmol/L (1.8%) for phosphomonoesters (PME), 1.37 ± 0.07 mmol/L (7.9%) for inorganic phosphate (Pi), 11.40 ± 0.96 mmol/L (2.9%) for phosphodiesters (PDE), and 2.14 ± 0.10 mmol/L (1.6%) for adenosine triphosphate (ATP), respectively. Taken together, this approach provides fast, simple, and reproducible high‐resolution absolute quantification and detailed mapping of the spatial distribution of hepatic 31P metabolites. This method allows for examination of regional deviations of energy metabolism in human liver diseases. Magn Reson Med 60:796–802, 2008. © 2008 Wiley‐Liss, Inc.
Design and use of tailored hard‐pulse trains for uniformed saturation of myocardium at 3 Tesla
Authors: Sung Kyunghyun , Nayak Krishna S.
Published: September 2008

Complete and uniform saturation of myocardium is essential for quantitative myocardial perfusion imaging using the first pass of a contrast agent. At 3 T, inhomogeneities of both the static (B0) and radiofrequency (B1) magnetic fields have led to the use of adiabatic B1‐insensitive rotation type 4 (BIR‐4) pulses, which in practice are constrained by radiofrequency (RF) heating. In this study, we propose the use of trains of weighted hard pulses that are optimized for the measured variation of B0 and B1 fields in the myocardium. These pulses are simple to design, and require substantially lower RF power when compared with BIR‐4 pulses. In volunteers, at 3 T, we demonstrated that the proposed saturation pulse with three subpulses results in lower peak and lower average residual longitudinal magnetization over the heart, as compared with 8‐msec BIR‐4 pulses and conventional hard pulse trains (P < 0.05). Magn Reson Med 60:997–1002, 2008. © 2008 Wiley‐Liss, Inc.
Transport phenomena in kaolinite clay: Molecular simulation, homogenization analysis and similitude law
Authors: Choi Jung Hae , Anwar A. H. M. Faisal , Kawamura Katsuyuki , Ichikawa Yasuaki
Published: September 2008

Kaolinite is a common clay mineral. It is a nanomaterial with a platelet crystalline structure. In order to analyze the behavior of kaolinite, its microscopic structure and material properties must be specified correctly. A molecular dynamics (MD) simulation is used for determining the microscale properties of hydrated kaolinite, and these properties are introduced into a multiscale homogenization analysis (HA). We previously developed such an MD/HA technique to investigate seepage, diffusion, sorption and consolidation in bentonite clay (Proceedings of the Science Basis for Nuclear Waste Management, Davos, Switzerland, vol. XXI. Material Research Society: Warrendale, PA, 1997; 359–366; Eng. Geol. 1999; 54:21–31; Eng. Geol. 2001; 60:127–138; Coupled Thermo‐Hydro‐Mechanical‐Chemical Processes in Geo‐systems. Elsevier: Amsterdam, 2005; 457–464). We here apply the method to kaolinite clay to investigate the permeability, diffusion and related similitude law. The obtained results are supported by existing experimental data. Copyright © 2008 John Wiley & Sons, Ltd.
Severe deficiency of coagulation Factor VII results in spontaneous cardiac fibrosis in mice
Authors: Xu H , Noria F , Sandoval‐Cooper MJ , Menchen H , Donahue DL , Ploplis VA , Castellino FJ
Published: September 2008

Mice genetically modified to produce low levels (∼1% of wild‐type) of coagulation FVII presented with echocardiographic evidence of heart abnormalities. Decreases in ventricular size and reductions in systolic and diastolic functions were found, suggestive of a restrictive cardiomyopathy and consistent with an infiltrative myopathic process. Microscopic analysis of mouse hearts showed severe patchy fibrosis in the low‐FVII mice. Haemosiderin deposition was discovered in hearts of these mice, along with increases in inflammatory cell number, ultimately resulting in widespread collagen deposition. Significant increases in mRNA levels of TGFβ, TNFα and several matrix metalloproteinases in low‐FVII mice, beginning at early ages, supported a state of cardiac remodelling associated with the fibrotic pathology. Mechanistic time‐course studies suggested that cardiac fibrosis in low‐FVII mice originated from bleeding in heart tissue, resulting in the recruitment of leukocytes, which released inflammatory mediators and induced collagen synthesis and secretion. These events led to necrosis of cardiomyocytes and collagen deposition, characteristics of cardiac fibrosis. The results of this study demonstrated that haemorrhagic and inflammatory responses to a severe FVII deficiency resulted in the development of cardiac fibrosis, observed echocardiographically as a restrictive cardiomyopathy, with compromised ventricular diastolic and systolic functions. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Bivalirudin for anticoagulation in children
Authors: Rayapudi Sobharani , Torres Adalberto , Deshpande Girish G. , Ross Mitchell P. , Wohrley Julie D. , Young Guy , Tarantino Michael D.
Published: September 2008

Background

Thromboembolism in children is typically treated with unfractionated heparin (UH) or low molecular weight heparin (LMWH). Both rely on antithrombin (AT) for their action. In addition, heparin‐induced thrombocytopenia (HIT) is a potentially serious complication of heparin use in children. Bivalirudin or other direct thrombin inhibitors may be a useful alternative to heparins in treating thrombosis in children.

Procedure

We report a retrospective review to assess the efficacy and safety of bivalirudin in pediatric patients with thrombosis.

Results

Sixteen children received bivalirudin for thrombosis or prevention of thrombosis at the Children's Hospital of Illinois from January 2005 to January 2007. Patients received a bolus dose of 0.25 mg/kg followed by a continuous infusion (0.16 ± 0.07 mg kg−1 hr−1) titrated to 1.5–2.5 times the baseline activated partial thromboplastin time (aPTT). Positive correlation between the bivalirudin average infusion rate and aPTT was observed in twelve patients. Ultrasonographic evidence of thrombus regression was noted at 72 hr in 10 of 10 patients. One patient experienced hematuria after catheterization of the urethra.

Conclusion

Bivalirudin was effective and well‐tolerated in these patients. Further studies should be conducted to better define safety and efficacy of bivalirudin in pediatric patients. Pediatr Blood Cancer 2008;51:798–801. © 2008 Wiley‐Liss, Inc.
Health‐related quality of life, cognitive functioning and behaviour problems in children with Langerhans cell histiocytosis
Authors: Vrijmoet‐Wiersma C.M. Jantien , Kooloos Vicky M. , Koopman Hendrik M. , Kolk Annemarie M. , van der Laan Ingrid , Grootenhuis Martha A. , Egeler R. Maarten
Published: September 2008

Background

This study was designed to evaluate generic and disease‐specific health‐related quality of life (HRQoL), cognitive functioning and behaviour problems of children with Langerhans Cell Histiocytosis (LCH). Furthermore, we investigated which medical determinants and social demographic factors were predictive for HRQoL, cognitive functioning and behavioural problems.

Procedure

In this cross‐sectional case‐control study 24 children ranging from 7 to 17 years of age were administered a HRQoL questionnaire, cognitive tests and behaviour ratings. In addition, a disease‐specific HRQoL measure was developed and tested. Results were compared to a reference group consisting of healthy peers and to proxy‐ratings by parents and teachers.

Results

Children with LCH reported a lower physical HRQoL than the reference group (P ≤ 0.05). Children older than 12 reported lower HRQoL scores. Scores on the disease‐specific HRQoL questionnaire were lower than on the generic measure used. Performances on cognitive tests varied widely, short term visual memory was most affected. Twenty‐five percent of the children follow special education. According to parents and teachers, children with LCH had more internalising behaviour problems (i.e., anxiety and depression), compared to the instrument norms. Children with Diabetes Insipidus, other CNS involvement and children who have had chemotherapy had more cognitive and behaviour problems than the other children with LCH.

Conclusions

HRQoL is affected in children with LCH, especially in older children. Children with LCH show more internalising problem behaviour than their peers. Teachers are important additional informants about behaviour problems. Pediatr Blood Cancer 2009;52:116–122. © 2008 Wiley‐Liss, Inc.
Pre‐ and post‐natal treatment of hemophagocytic lymphohistiocytosis
Authors: Shah Ami J. , Kapoor Neena , Cooper Robert M. , Crooks Gay M. , Lenarsky Carl , Abdel‐Azim Hisham , Wu Shi Qi , Wilson Kathy , Weinberg Kenneth I. , Parkman Robertson , Kohn Donald B.
Published: September 2008

Hemophagocytic lymphohistiocytosis (HLH) is a rare autosomal recessive disorder of infancy and childhood that is invariably fatal if not treated. We report on the first patient to receive post‐natal HSCT for HLH after receiving in utero chemotherapy for disease stabilization. Pediatr Blood Cancer 2009;52:139–142. © 2008 Wiley‐Liss, Inc.
Use of digitoxin and digoxin as internal standards in HPLC analysis of triterpene saponin‐containing extracts
Authors: Balsevich J. John , Bishop Greg G. , Deibert Leah K.
Published: September 2008

Introduction

Saponins are widely distributed complex plant glycosides possessing a variety of structure‐dependent bioactivities. Quantitation of individual saponins is difficult due to lack of available standards, mainly as a consequence of purification difficulties. Determination of total saponin content can be problematic, often relying on non‐specific methods based on butanol solubility, haemolytic activity or formation of coloured derivatives.

Objective

To develop a general quantitative method based on the use of the readily available cardenolides, digitoxin (1) and digoxin (2), as internal standards in an HPLC‐PAD‐based analysis.

Methodology

The cardenolides were run at a variety of concentrations to establish linearity and reproducibility of detector response and then evaluated as internal standards for quantitation of triterpene saponins in several plant‐derived extracts by HPLC‐PAD. Mixtures of saponins, largely freed from other extractables, were obtained by fractionation of total extracts on solid phase extraction columns (SPE) employing a water–methanol gradient and used for construction of calibration curves. Saponin identification and structural information was obtained via a single quadrupole mass detector using electrospray ionisation in negative ion mode (ESI−).

Results

Saponin contents in six samples from five species were determined and compared with literature results and a gravimetric method based on butanol–water partitioning. Results were generally consistent with literature reports and superior to gravimetric butanol–water partitioning.

Conclusion

Digitoxin and digoxin are useful as internal standards in HPLC estimation of saponin content. Saponins from different species having similar structures and molecular weights afford similar calibration curves. Copyright © 2008 John Wiley & Sons, Ltd.
Smart sunglasses based on electrochromic polymers
Authors: Ma Chao , Taya Minoru , Xu Chunye
Published: September 2008

Smart sunglasses based on electrochromic polymers are proposed and developed in this study. This article discusses the design, processing, and the optical and electrical performance of a prototype smart sunglasses based on cathodic electrochromic (EC) polymers, which show several merits compared with traditional materials for sunglasses lens as well as other smart window materials. It is a multilayer design of device. The conjugated polymer, poly[3,3‐dimethyl‐3,4‐dihydro‐2H‐thieno [3,4‐b] [1,4]dioxepine] (PProDOT‐Me2), is utilized as the electrochromic working layer. The counter layer of the device is vanadium oxide (V2O5) film, which serves as an ion storage layer. There is also a polymer gel electrolyte acting as the ionic transport layer, sandwiched between the working and counter layers. The characteristics of the prototype device are reported, including transmittance (%T), driving power, response time, open circuit memory, and lifetime. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers
Characterizing the nonlinear viscoelastic properties of sealant, including its Mullins effect
Authors: White C.C. , Hunston D.L.
Published: September 2008

Quantification of mechanical properties, such as nonlinear viscoelastic behavior, for a cured sealant is complicated by the presence of the Mullins effect. This article examines the mechanical behavior of five different sealants materials encompassing the range of currently available commercial sealant formulations. The Mullins effect was observed for all materials and was present in both tensile and compression experiments. If a previously tested sample was allowed to rest (remain unloaded) for a sufficiently long period of time, however, the Mullins effect was partially recovered; that is, the modulus measured during the first mechanical loading following the rest period was greater than that obtained on subsequent loadings. Samples were then preloaded to remove the Mullins effect, and their nonlinear viscoelastic properties were examined using stress–relaxation experiments. Although the behavior was complex, the time and strain dependences were sufficiently independent so that time–strain superposition could be used to simplify modeling and characterization without introducing significant errors. A simple empirical equation was formulated to describe the behavior for all five sealants over the range of strains and time scales examined. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers
HDPE functionalization via high shear stress‐induced initiation and its effects on HDPE/GF composite
Authors: Zhang Yuncan , Chen Jinyao , Li Huilin
Published: September 2008

The functionalization reaction of high density polyethylene (HDPE) with maleic anhydride (MAH) or with MAH and γ‐methacryloxy‐propyltrimethoxysilane (MAS) performed in melt state through a high shear stress‐induced initiation by increasing the screw rotation speed of twin‐screw extruder and through a compounded initiation by adding some initiator and increasing the screw rotation speed was investigated in this article. The results show that by increasing the screw rotation speed during melt‐extruding process, the scission of HDPE chain bonds can be caused to form macroradicals, the functionalization reaction of HDPE with MAH or with MAH, and MAS can be realized. The percentage of grafting and the melt flow rate of the functionalized products depend on the screw rotation speed and reaction temperature. The crosslinking reaction during melt extrusion can be suppressed by increasing the screw rotation speed and the reaction of HDPE with MAH can also be promoted by adding a second grafting monomer MAS. The high shear stress‐induced reaction products have a higher reactivity with the coupling agents coated on the surface of glass fibers and can obviously increase the mechanical properties of HDPE/GF composite. The SEM experimental results indicate that an oriented crystal transition layer exists between the interface of glass fiber and the matrix, the interfacial bonding strength is the determining factor of the formation of the oriented crystal layer. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers
An optical investigation of high‐tenacity polyester (H‐T PET) fibers annealed at different temperatures
Authors: El‐Dessouky H.M. , Mahmoudi M.R. , Yassien K.M. , Lawrence C.A.
Published: September 2008

A two‐beam “Interphako” interference microscope was used to study the effect of annealing on the physical properties of high‐tenacity poly(ethylene terephthalate) H‐T PET fibers. The PET fibers were annealed with free ends for 1 h at temperatures ranging from 100 to 200°C. The shrinkage, refractive indices, and orientation angle of the PET fibers were determined for different annealing temperatures. The measured birefringence and orientation function were found to have decreased with increasing temperature, whereas the degree of crystallinity and the onset temperature (DSC) increased. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers
Novel mesogen‐jacketed poly(p‐phenylenevinylene) derivatives bearing oxadiazole pendants: Design, synthesis, and optoelectronic properties
Authors: Sun Limei , Wang Ping , Jin Hao , Fan Xinghe , Shen Zhihao , Chen Xiaofang , Zhou Qi‐Feng
Published: September 2008

1,3,4‐oxadiazole moieties were laterally linked to the phenyl rings via a short OCH2 spacer and a series of novel poly(p‐phenylenevinylene) derivatives have been successfully synthesized through Horner–Witting–Emmons coupling reaction. The structures and properties of the monomers and the resulting conjugated polymers were characterized by nuclear magnetic resonance spectroscope, Fourier transform infrared, elemental analysis, gel permeation chromatography, thermogravimetric analysis, UV–vis absorption (UV) spectroscopy, photoluminescence spectroscopy and cyclic voltammetry. The UV spectra at solution state was similar to what's observed at film state while the PL spectra at film state had a red shift from 19 to 28 nm compared with the results at solution state, which implied that the unique bulky jacketed structure containing oxadiazole unit of these copolymers could effectively suppress π‐stacking/aggregation. LUMO levels of these polymers varied from −3.44 to −3.63 eV with increasing content of oxadiazole units, which facilitated electron injection. PLEDs with the configuration of ITO/PEDOT/Polymer/TPBI (15 nm)/LiF (1 nm)/Al (100 nm) were fabricated, which emit a yellowish green light around 540 and 570 nm with a maximum brightness of 1074.7 cd/m2 and luminous efficiency of 0.108 cd/A. The introduction of the unique bulky OXD unit into PPVs at a low molar content largely improved the electroluminescence properties of PPV. © Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7173–7186, 2008
“Click” coupling between alkyne‐decorated multiwalled carbon nanotubes and reactive PDMA‐PNIPAM micelles
Authors: Liu Jinyao , Nie Zhihua , Gao Yong , Adronov Alex , Li Huaming
Published: September 2008

Covalent functionalization of alkyne‐decorated multiwalled carbon nanotubes (MWNTs) with a well‐defined, azide‐derivatized, thermoresponsive diblock copolymer, poly(N,N‐dimethylacrylamide)‐poly(N‐isopropylacrylamide) (PDMA‐PNIPAM) was accomplished by the Cu(I)‐catalyzed [3 + 2] Huisgen cycloaddition. It was found that this reaction could simultaneously increase the molecular size and bonding density of grafted polymers when PDMA‐PNIPAM micelles were employed in the coupling system. On the other hand, attachment of molecularly dissolved unimers of high‐molecular weight onto the nanotube resulted in low‐graft density. The block copolymer bearing azide groups at the PDMA end was prepared by reversible addition–fragmentation transfer polymerization, which formed micelles with a diameter of ∼40 nm at temperatures above its critical micelle temperature. Scanning electron microscopy was utilized to demonstrate that the coupling reaction was successfully carried out between copolymer micelles and alkyne‐bearing MWNTs. FTIR spectroscopy was utilized to follow the introduction and consumption of alkyne groups on the MWNTs. Thermogravimetric analysis indicated that the functionalized MWNTs consisted of about 45% polymer. Transmission electron microscopy was utilized to image polymer‐functionalized MWNTs, showing relatively uniform polymer coatings present on the surface of nanotubes. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7187–7199, 2008
Stability and utility of pyridyl disulfide functionality in RAFT and conventional radical polymerizations
Authors: Boyer Cyrille , Liu Jingquan , Wong Lingjiun , Tippett Michael , Bulmus Volga , Davis Thomas P.
Published: September 2008

Two RAFT agents, suitable for inducing living radical polymerization in water, have been synthesized. Both RAFT agents were shown to be effective over the temperature range 25–70 °C. One RAFT agent was functionalized with a pyridyl disulfide group. RAFT efficacy was demonstrated for the polymerizations of N‐isopropyl acrylamide (NIPAAM) and poly(ethylene oxide)‐acrylate (PEG‐A) in both water and acetonitrile. The kinetic data indicates that the pyridyl disulfide functionality is largely benign in free radical polymerizations, remaining intact for subsequent reaction with thiol groups. This result was confirmed by studying conventional radical polymerizations in the presence of hydroxyethyl pyridyl disulfide. The utility of the pyridyl disulfide functionality at the terminus of the polymers was demonstrated by synthesizing polymer‐BSA conjugates. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7207–7224, 2008
Polyelectrolyte‐grafted carbon nanotubes: Synthesis, reversible phase‐transition behavior, and tribological properties as lubricant additives
Authors: Pei Xiaowei , Xia Yanqiu , Liu Weimin , Yu Bo , Hao Jingcheng
Published: September 2008

A novel polyelectrolyte‐grafted multiwalled carbon nanotubes (MWCNTs‐g‐PILs) which possesses a hard backbone of MWCNTs and a soft shell of brush‐like poly (ionic liquids) (PILs) has been synthesized via the surface atom transfer radical polymerization (ATRP). Chemical structure and the grafted PILs quantities of MWCNTs‐g‐PILs were determined by FTIR, TGA, and XPS. TEM and FE‐SEM observations indicate that the nanotubes were coated with a PILs layer, exhibiting core‐shell nanostructures with the PILs chains as the brush‐like or hairy shell and the MWCNTs as the hard backbone. Furthermore, the effect of counter‐anions on the solubility of MWCNTs‐g‐PILs was investigated. The results indicate that relative solubility of MWCNTs‐g‐PILs in various solvents could be switched by anion exchange. This tunable solubility results in the formation of the cycle of reversible phase‐transition. Tribological property of MWCNTs‐g‐PILs as additives in base lubricant 1‐methyl‐3‐butylimidaaolium hexafluorophosphate (LP104) was evaluated using an Optimol SRV oscillating friction and wear tester, confirming that MWCNTs‐g‐PILs are the excellent antiwear and friction‐reducing additives, which can amend the tribological properties of base lubricant significantly. This is attributed to the good dispersibility and core‐shell structure of MWCNTs‐g‐PILs. These results reported in this work may open primarily toward constructing a bridge among carbon nanotues (CNTs), ILs, and lubricant additives and secondarily to prove that CNTs (modified CNTs) as lubricant additives are promising candidates. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7225–7237, 2008
Synthesis of homopolymers and copolymers containing an active ester of acrylic acid by RAFT: Scaffolds for controlling polyvalent ligand display
Authors: Gujraty Kunal V. , Yanjarappa Mallinamadugu J. , Saraph Arundhati , Joshi Amit , Mogridge Jeremy , Kane Ravi S.
Published: September 2008

We describe the synthesis of activated homopolymers and copolymers of controlled molecular weight based on the controlled radical polymerization of N‐acryloyloxysuccinimide (NAS) by reversible addition fragmentation chain transfer (RAFT). We synthesized activated homopolymers in a range of molecular weights with polydispersities between 1 and 1.2. The attachment of an inhibitory peptide to the activated polymer backbone yielded a potent controlled molecular weight polyvalent inhibitor of anthrax toxin. To provide greater control over the placement of the peptides along the polymer backbone, we also used a semibatch copolymerization method to synthesize copolymers of NAS and acrylamide (AAm). This approach enabled the synthesis of copolymers with control over the placement of peptide‐reactive NAS monomers along an inert backbone; subsequent functionalization of NAS with peptide yielded well‐defined polyvalent anthrax toxin inhibitors that differed in their potencies. These strategies for controlling molecular weight, ligand density, and ligand placement will be broadly applicable for designing potent polyvalent inhibitors for a variety of pathogens and toxins and for elucidating structure–activity relationships in these systems. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7249–7257, 2008
In situ intercalative polymerization of conducting polypyrrole/montmorillonite nanocomposites
Authors: Karim Mohammad Rezaul , Yeum Jeong Hyun
Published: September 2008

Conducting polypyrrole (PPy)‐montmorillonite (MMT) clay nanocomposites have been synthesized by the in situ intercalative polymerization method. The PPy‐MMT nanocomposites are characterized by field‐emission scanning electron microscopy (FE‐SEM), transmission electron microscopy (TEM), X‐ray diffraction (XRD), ultraviolet–visible (UV–vis) spectroscopy, thermogravimetric analysis (TGA), and Fourier‐transform infrared (FTIR) spectroscopy. XRD patterns show that after polymerization by the in situ intercalative method with ammonium persulfate and 1 M HCl, an increase in the basal spacing from 1.2 to 1.9 nm was observed, signifying that PPy is synthesized between the interlayer spaces of MMT. TEM and SEM micrographs suggest that the coexistence of intercalated MMT layers with the PPy macromolecules. FTIR reveals that there might be possible interfacial interactions present between the MMT clay and PPy matrix. The study also shows that the introduction of MMT clay results in thermal stability improvement of the PPy. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 2279–2285, 2008
Poly(ethylene imine)‐graft‐poly(ethylene oxide) brush‐like copolymers: Preparation, thermal properties, and selective supramolecular inclusion complexation with α‐cyclodextrin
Authors: Li Lei , Zheng Sixun
Published: September 2008

Poly(ethylene imine)‐graft‐poly(ethylene oxide) (PEI‐g‐PEO) copolymers were synthesized via Michael addition reaction between acryl‐terminated poly(ethylene oxide) methyl ether (PEO) and poly(ethylene imine) (PEI). The brush‐like copolymers were characterized by means of Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. It is found that the crystallinity of the PEO side chains in the copolymers remained unaffected by the PEI backbone whereas the crystal structure of PEO side chains was altered to some extent by the PEI backbone. The crystallization behavior of PEO blocks in the copolymers suggests that the bush‐shaped copolymers are microphase‐separated in the molten state. The PEO side chains of the copolymers were selectively complexed with α‐cyclodextrin (α‐CD) to afford hydrophobic side chains (i.e., PEO/α‐CD inclusion complexes). The X‐ray diffraction (XRD) shows that the inclusion complexes (ICs) of the PEO side chains displayed a channel‐type crystalline structure. It is identified that the stoichiometry of the inclusion complexation of the PEI‐g‐PEO with α‐CD is close to that of the control PEO with α‐CD. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 2296–2306, 2008
Chemorheology of photopolymerizable acrylates using a modified Boltzmann sigmoidal model
Authors: Love B. J. , Ruinet F. Piguet , Teyssandier F.
Published: September 2008

Experiments were conducted to evaluate the influence of ambient photoconversion on rheology for a range of photopolymerizable urethane dimethacrylate (UDMA) resins containing varying amounts of three comonomers including 1,6 hexane diol‐dimethacrylate (HDDMA), an alkoxylated cyclohexane dimethanol diacrylate monomer (CD‐582), and hydroxyethyl methacrylate (HEMA). Experiments were performed both as a function of composition and time‐dependent dose varying the intensity using a photorheometer. A semilog‐based sigmoidal model allowed the determination of four physical model parameters to define the relationship between reaction kinetics and its dynamic influence on viscosity. We have observed induction times and viscosity changes associated with the model that shows a trend in reaction kinetics in the following order from most to least reactive: UDMA > CD582 > HDDMA > HEMA. With increasing amounts of reactive diluent included in the formulation, the kinetics of reaction was more sluggish. The value of this sigmoidal model is that it could help define formulation and process conditions most likely to control crosslinking to maximize dimensional stability or other thermophysical properties. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 2319–2325, 2008
The accumulation of versican in the nodules of benign prostatic hyperplasia
Authors: True Lawrence D. , Hawley Sarah , Norwood Thomas H. , Braun Kathleen R. , Evanko Stephen P. , Chan Christina K. , LeBaron Richard C. , Wight Thomas N.
Published: September 2008

BACKGROUND

Proteoglycans, a complex group of extracellular matrix (ECM) molecules, are elevated in benign prostatic hyperplasia (BPH). Versican is a stromal proteoglycan present in prostate tissue. Versican expression is elevated in tissues with increased proliferation. Based on these observations, we determined the extent and distribution of versican expression in prostates with BPH.

METHODS

The involvement of versican in BPH nodules was compared with levels in non‐nodular transition (TZ) and peripheral zone (PZ) tissues from 18 human prostate glands using immunohistochemistry, Northern blots and/or QRTPCR to localize versican and quantify versican mRNA transcript levels, and Western blots to assess gene product levels.

RESULTS

Increased versican immunoreactivity was observed in the stroma of BPH nodules. Higher steady state levels of versican variants V0, V1, and V3 mRNA transcript and gene product were detected in the nodular tissues than in the non‐nodular TZ or PZ parenchyma.

CONCLUSIONS

These results suggest that versican may play a role in nodule formation in BPH. Prostate 69: 149–158, 2009. © 2008 Wiley–Liss, Inc.
Inflammatory processes of prostate tissue microenvironment drive rat prostate carcinogenesis: Preventive effects of celecoxib
Authors: Narayanan Narayanan K. , Nargi Dominick , Horton Lori , Reddy Bandaru S. , Bosland Maarten C. , Narayanan Bhagavathi A.
Published: September 2008

BACKGROUND

Prostate tissue microenvironment is susceptible to several risk factors including carcinogens, dietary factors, hormones, cytokines and growth factors that could induce chronic inflammation. Because of the difference in the serum levels and the intrinsic ability of monocytes/macrophages to cause harm, the transcriptional responses triggered by inflammatory stimuli must be controlled. Unfortunately, an in‐depth association between prostate cancer and potential mediators of inflammation has not been completely investigated.

METHODS

To determine whether activated macrophage (infiltrating monocytes), iNOS and NF‐κB are primary mediators of inflammation, besides COX‐2, in prostate carcinogenesis, we examined tissue sections of rat prostate tumor induced by N‐methyl‐N‐nitrosourea (MNU) plus testosterone in a follow‐up study. We performed H&E and immunohsitochemical staining of the prostate tissue to detect specific markers of inflammation.

RESULTS

We report an increase in infiltrating monocyte, iNOS, NF‐κBp65, VEGF and TNF‐α at the early and advanced stages of tumor growth in MNU plus testosterone treated rats. Monocyte infiltration was often found in the stromal and perivascular regions of the DL prostate. We conclude for the first time that prostate cancer induced by MNU plus testosterone partly involves mediators of inflammation which could trigger the process of carcinogenesis and cause loss of apoptosis. Selective COX‐2 inhibitor celecoxib at a dose of 500 mg/kg/bw administered for 52 weeks reduced infiltrating monocytes, inhibited iNOS, NF‐κB p65 expression, induced apoptosis and tumor growth inhibition.

CONCLUSION

Carcinogen plus testosterone induced prostate carcinogenesis showing activation of macrophage, iNOS and NF‐κBp65 could be prevented by celecoxib or related anti‐inflammatory agents. Prostate 69: 133–141, 2009. © 2008 Wiley–Liss, Inc.
Trapping open and closed forms of FitE—A group III periplasmic binding protein
Authors: Shi Rong , Proteau Ariane , Wagner John , Cui Qizhi , Purisima Enrico O. , Matte Allan , Cygler Miroslaw
Published: September 2008

Periplasmic binding proteins (PBPs) are essential components of bacterial transport systems, necessary for bacterial growth and survival. The two‐domain structures of PBPs are topologically classified into three groups based on the number of crossovers or hinges between the globular domains: group I PBPs have three connections, group II have two, and group III have only one. Although a large number of structures for group I or II PBPs are known, fewer group III PBPs have been structurally characterized. Group I and II PBPs exhibit significant domain motions during transition from the unbound to ligand‐bound form, however, no large conformational changes have been observed to date in group III PBPs. We have solved the crystal structure of a periplasmic binding protein FitE, part of an iron transport system, fit, recently identified in a clinical E. coli isolate. The structure, determined at 1.8 Å resolution, shows that FitE is a group III PBP containing a single α‐helix bridging the two domains. Among the individual FitE molecules present in two crystal forms we observed three different conformations (open, closed, intermediate). Our crystallographic and molecular dynamics results strongly support the notion that group III PBPs also adopt the same Venus flytrap mechanism as do groups I and II PBPs. Unlike other group III PBPs, FitE forms dimers both in solution and in the crystals. The putative siderophore binding pocket is lined with arginine residues, suggesting an anionic nature of the iron‐containing siderophore. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Unifying mechanical and thermodynamic descriptions across the thioredoxin protein family
Authors: Mottonen James M. , Xu Minli , Jacobs Donald J. , Livesay Dennis R.
Published: September 2008

We compare various predicted mechanical and thermodynamic properties of nine oxidized thioredoxins (TRX) using a Distance Constraint Model (DCM). The DCM is based on a nonadditive free energy decomposition scheme, where entropic contributions are determined from rigidity and flexibility of structure based on distance constraints. We perform averages over an ensemble of constraint topologies to calculate several thermodynamic and mechanical response functions that together yield quantitative stability/flexibility relationships (QSFR). Applied to the TRX protein family, QSFR metrics display a rich variety of similarities and differences. In particular, backbone flexibility is well conserved across the family, whereas cooperativity correlation describing mechanical and thermodynamic couplings between the residue pairs exhibit distinctive features that readily standout. The diversity in predicted QSFR metrics that describe cooperativity correlation between pairs of residues is largely explained by a global flexibility order parameter describing the amount of intrinsic flexibility within the protein. A free energy landscape is calculated as a function of the flexibility order parameter, and key values are determined where the native‐state, transition‐state, and unfolded‐state are located. Another key value identifies a mechanical transition where the global nature of the protein changes from flexible to rigid. The key values of the flexibility order parameter help characterize how mechanical and thermodynamic response is linked. Variation in QSFR metrics and key characteristics of global flexibility are related to the native state X‐ray crystal structure primarily through the hydrogen bond network. Furthermore, comparison of three TRX redox pairs reveals differences in thermodynamic response (i.e., relative melting point) and mechanical properties (i.e., backbone flexibility and cooperativity correlation) that are consistent with experimental data on thermal stabilities and NMR dynamical profiles. The results taken together demonstrate that small‐scale structural variations are amplified into discernible global differences by propagating mechanical couplings through the H‐bond network. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Structure of the S1S2 glutamate binding domain of GLuR3
Authors: Ahmed Ahmed H. , Wang Qi , Sondermann Holger , Oswald Robert E.
Published: September 2008

Glutamate receptors are the most prevalent excitatory neurotransmitter receptors in the vertebrate central nervous system. Determining the structural differences between the binding sites of different subtypes is crucial to our understanding of neuronal circuits and to the development of subtype specific drugs. The structures of the binding domain (S1S2) of the GluR3 (flip) AMPA receptor subunit bound to glutamate and AMPA and the GluR2 (flop) subunit bound to glutamate were determined by X‐ray crystallography to 1.9, 2.1, and 1.55 Å, respectively. Overall, the structure of GluR3 (flip) S1S2 is very similar to GluR2 (flop) S1S2 (backbone RMSD of 0.30 ± 0.05 for glutamate‐bound and 0.26 ± 0.01 for AMPA‐bound). The differences in the flip and flop isoforms are subtle and largely arise from one hydrogen bond across the dimer interface and associated water molecules. Comparison of the binding affinity for various agonists and partial agonists suggest that the S1S2 domains of GluR2 and GluR3 show only small differences in affinity, unlike what is found for the intact receptors (with the exception of one ligand, Cl‐HIBO, which has a 10‐fold difference in affinity for GluR2 vs. GluR3). Proteins 2009. © 2008 Wiley‐Liss, Inc.
Backbone conformations and side chain flexibility of two somatostatin mimics investigated by molecular dynamics simulations
Authors: Interlandi Gianluca
Published: September 2008

Molecular dynamics simulations with two designed somatostatin mimics, SOM230 and SMS 201‐995, were performed in explicit water for a total aggregated time of 208 ns. Analysis of the runs with SOM230 revealed the presence of two clusters of conformations. Strikingly, the two sampled conformers correspond to the two main X‐ray structures in the asymmetric unit of SMS 201‐995. Structural comparison between the residues of SOM230 and SMS 201‐995 provides an explanation for the high binding affinity of SOM230 to four of five somatostatin receptors. Similarly, cluster analysis of the simulations with SMS 201‐995 shows that the backbone of the peptide interconverts between its two main crystallographic conformers. The conformations of SMS 201‐995 sampled in the two clusters violated two different sets of NOE distance constraints in agreement with a previous NMR study. Differences in side chain fluctuations between SOM230 and SMS 201‐995 observed in the simulations may contribute to the relatively higher binding affinity of SOM230 to most somatostatin receptors. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Accurate prediction for atomic‐level protein design and its application in diversifying the near‐optimal sequence space
Authors: Fromer Menachem , Yanover Chen
Published: September 2008

The task of engineering a protein to assume a target three‐dimensional structure is known as protein design. Computational search algorithms are devised to predict a minimal energy amino acid sequence for a particular structure. In practice, however, an ensemble of low‐energy sequences is often sought. Primarily, this is performed because an individual predicted low‐energy sequence may not necessarily fold to the target structure because of both inaccuracies in modeling protein energetics and the nonoptimal nature of search algorithms employed. Additionally, some low‐energy sequences may be overly stable and thus lack the dynamic flexibility required for biological functionality. Furthermore, the investigation of low‐energy sequence ensembles will provide crucial insights into the pseudo‐physical energy force fields that have been derived to describe structural energetics for protein design. Significantly, numerous studies have predicted low‐energy sequences, which were subsequently synthesized and demonstrated to fold to desired structures. However, the characterization of the sequence space defined by such energy functions as compatible with a target structure has not been performed in full detail. This issue is critical for protein design scientists to successfully continue using these force fields at an ever‐increasing pace and scale. In this paper, we present a conceptually novel algorithm that rapidly predicts the set of lowest energy sequences for a given structure. Based on the theory of probabilistic graphical models, it performs efficient inspection and partitioning of the near‐optimal sequence space, without making any assumptions of positional independence. We benchmark its performance on a diverse set of relevant protein design examples and show that it consistently yields sequences of lower energy than those derived from state‐of‐the‐art techniques. Thus, we find that previously presented search techniques do not fully depict the low‐energy space as precisely. Examination of the predicted ensembles indicates that, for each structure, the amino acid identity at a majority of positions must be chosen extremely selectively so as to not incur significant energetic penalties. We investigate this high degree of similarity and demonstrate how more diverse near‐optimal sequences can be predicted in order to systematically overcome this bottleneck for computational design. Finally, we exploit this in‐depth analysis of a collection of the lowest energy sequences to suggest an explanation for previously observed experimental design results. The novel methodologies introduced here accurately portray the sequence space compatible with a protein structure and further supply a scheme to yield heterogeneous low‐energy sequences, thus providing a powerful instrument for future work on protein design. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Mechanical stability and differentially conserved physical–chemical properties of titin Ig‐domains
Authors: Garcia Tzintzuni I. , Oberhauser Andres F. , Braun Werner
Published: September 2008

The mechanisms that determine mechanical stabilities of protein folds remain elusive. Our understanding of these mechanisms is vital to both bioengineering efforts and to the better understanding and eventual treatment of pathogenic mutations affecting mechanically important proteins such as titin. We present a new approach to analyze data from single‐molecule force spectroscopy for different domains of the giant muscle protein titin. The region of titin found in the I‐band of a sarcomere is composed of about 40 Ig‐domains and is exposed to force under normal physiological conditions and connects the free‐hanging ends of the myosin filaments to the Z‐disc. Recent single‐molecule force spectroscopy data show a mechanical hierarchy in the I‐band domains. Domains near the C‐terminus in this region unfold at forces two to three times greater than domains near the beginning of the I‐band. Though all of these Ig‐domains are thought to share a fold and topology common to members of the Ig‐like fold family, the sequences of neighboring domains vary greatly with an average sequence identity of only 25%. We examine in this study the relation of these unique mechanical stabilities of each I‐band Ig domain to specific, conserved physical–chemical properties of amino acid sequences in related Ig domains. We find that the sequences of each individual titin Ig domain are very highly conserved, with an average sequence identity of 79% across species that are divergent as humans, chickens, and zebra fish. This indicates that the mechanical properties of each domain are well conserved and tailored to its unique position in the titin molecule. We used the PCPMer software to determine the conservation of amino acid properties in titin Ig domains grouped by unfolding forces into “strong” and “weak” families. We found two motifs unique to each family that may have some role in determining the mechanical properties of these Ig domains. A detailed statistical analysis of properties of individual residues revealed several positions that displayed differentially conserved properties in strong and weak families. In contrast to previous studies, we find evidence that suggests that the mechanical stability of Ig domains is determined by several residues scattered across the β‐sandwich fold, and force sensitive residues are not only confined to the A′‐G region. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Unusual role of the substrate in droplet‐induced GaAs/AlGaAs quantum‐dot pairs
Authors: Wang Zh. M. , Mazur Yu. I. , Sablon K. A. , Mishima T. D. , Johnson M. B. , Salamo G. J.
Published: September 2008

The structural complexity of GaAs quantum‐dot pairs has been revealed by cross‐sectional transmission electron microscopy. As a result of high‐temperature droplet epitaxy, the AlGaAs substrate beneath the quantum‐dot pairs is no longer immobile and its reconstruction is observed to define the crystallization of gallium droplets under an arsenic flux. The GaAs quantum‐dot pairs are immersed into the substrate and further confined by the re‐distributed AlGaAs materials above the substrate plane. There are two underlying mechanisms responsible for the final nanostructure configuration, melt‐back etching by the gallium droplets and preferential crystallization of gallium around reconstructed sidewalls. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)