bluuebunny/crossref_metadata_2025 huggingface dataset:
Nuclear Spin Relaxation Parameters of MRI Contrast Agents – Insight from Quantum Mechanical Calculations
Authors: Yazyev Oleg V. , Helm Lothar
Published: December 2007

Nuclear magnetic relaxation in the presence of paramagnetic centres has gained increasing interest in recent years partly due to its importance for contrast agents in magnetic resonance imaging. Rational design of new more efficient agents is possible as a result of a better understanding of the underlying relaxation mechanisms. Quantum chemical calculations together with molecular dynamics simulations allow obtaining fundamental parameters such as quadrupole coupling constants and hyperfine interaction tensors directly at a molecular level. Recent results are presented on gadolinium(III) ions in aqueous solution and on [Gd(DOTA)(H2O)]–, a commercial MRI contrast agent. Isotropic hyperfine coupling constants can be calculated for 17O and 1H nuclear spins of water molecules in the first and second coordination sphere of Gd3+. It is also shown that the commonly used point‐dipole approximation for the dipolar interaction between the electron and the nuclear spin is in general valid for 1H spin but not for the directly bound 17O spin. The calculated quadrupole coupling parameters allow a direct determination of the rotational correlation time of complexes from the 17O nuclear spin relaxation.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Synthesis and Complexation Properties of Allenic Bipyridines, a New Class of Axially Chiral Ligands for Transition Metal Catalysis
Authors: Löhr Sandra , Averbeck Jan , Schürmann Markus , Krause Norbert
Published: December 2007

The allenic bipyridines 3, which represent a new class of axially chiral ligands for transition metal catalysis, were synthesized and their complexation properties were studied. The synthesis was achieved by copper‐mediated or palladium‐catalyzed SN2′‐substitution of the tertiary propargyl acetates 2. The allenic bipyridines form 1:1 complexes with Cu+ and Ag+ ions that were characterized by electrospray mass spectrometry and temperature‐dependent NMR spectroscopy. In the case of the C2‐symmetrical allene 3b, a crystalline silver complex was isolated that exists as a 2:2‐(L2M2) complex in the solid state.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Small Steric Variations in Ligands with Large Synthetic and Structural Consequences
Authors: Qayyum Sadaf , Haberland Kristina , Forsyth Craig M. , Junk Peter C. , Deacon Glen B. , Kempe Rhett
Published: December 2007

The reaction of ytterbium metal with the aminopyridines2,6‐(diisopropylphenyl)‐[6‐(2,6‐dimethylphenyl)pyridin‐2‐yl]amine (1, Ap′H) and (2,4,6‐trimethylphenyl)‐[6‐(2,4,6‐trimethylphenyl)pyridin‐2‐yl]amine (2, ApMeH) at elevated temperature under vacuum in the presence of mercury gave rise to divalent [Yb(Ap′)2] (3) and trivalent [Yb(ApMe)3] (4), respectively. The single‐crystal X‐ray structure analysis of 3 revealed a four‐coordinate ytterbium atom with two chelating (N,N′) Ap′ ligands inclined to each other at an angle of 126.93(7)° (Cl–Yb–C26). Additionally the complex forms intermolecular CAryl–H agostic interactions [Yb1···C17 2.981(2) Å and Yb1···H17 2.56(3) Å] (all H atoms refined). Complex 4 contains a six‐coordinate ytterbium atom having three chelating (N,N′) ApMe ligands and has distorted octahedral stereochemistry. The reaction of the potassium salts of Ap′H (5) and ApMeH (6) with [YbI2 (thf)4] in thf gave rise to the divalent lanthanoid complexes [Yb(Ap′)2(thf)] (7), and [Yb(ApMe)2(thf)2] (8), respectively, and 7 was also obtained by redox transmetallation/ligand exchange from Yb metal, HgPh2 and Ap′H. X‐ray crystal structures show that 7 and 8 have five‐ and six‐coordinate ytterbium atoms and distorted trigonal‐bipyramidal and distorted octahedral stereochemistry, respectively, the difference in coordination number reflecting the difference in steric demand of the Ap′ and ApMe ligands.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Efficient Stereoselective Syntheses of Constrained Glutamates via Michael‐Induced Ring Closing Reactions
Authors: Schmidt Christian , Kazmaier Uli
Published: December 2007

Zn‐chelated glycine ester enolates are highly efficient nucleophiles for the synthesis of conformationally constrained glutamates via domino sequences of Michael additions and subsequent ring closures (MIRC). This protocol allows the generation of 3–6‐membered ring systems in high yields and excellent diastereoselectivities. Depending on the reaction conditions either carbocyclic or heterocyclic ring systems are obtained. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Detection of single‐base mutations using 1‐D microfluidic beads array
Authors: Zhang He , Yang Xiaohai , Wang Kemin , Tan Weihong , Zhou Leiji , Zuo Xinbing , Wen Jianhui , Chen Yunqing
Published: December 2007

The application of a 1‐D microfluidic beads array that is composed of individually addressable functionalized SiO2 beads has been demonstrated for detection of single‐base mutations based on “sandwich” hybridization assay without additional sample labeling and PCR amplification. We concentrated on detection of mutations in the human p53 tumor suppressor gene with more than 50% mutation frequency in the known human cancers. Using a microinjection system, functionalized beads could be selectively and linearly arrayed in a single microfluidic channel comprising many periodic chambers. This 1‐D microfluidic beads array was sufficiently sensitive to identify single‐nucleotide mutations in 40 pM quantities of DNA targets and could discriminate the mutated alleles in an excess of nonmutated alleles at a level of one mutant in 100 wild‐type sequences. The surface of beads was regenerated and rehybridized up to six times without obvious loss of signal. The entire reaction process was done at room temperature within minutes, and only 2–10 μL sample solution was needed to complete the whole detection process. The p53 genotypes of A549, CNE2, and SKBr‐3 cell lines were also correctly evaluated by using mRNA extracts as target without need for sample labeling and amplification. Thus, this platform enabled rapid and exact discrimination of gene mutations with the advantages of reusability, simple handling of liquid, low cost, and little reagent consumption.
Channel wall coating on a poly‐(methyl methacrylate) CE microchip by thermal immobilization of a cellulose derivative for size‐based protein separation
Authors: Okada Hiroki , Kaji Noritada , Tokeshi Manabu , Baba Yoshinobu
Published: December 2007

We demonstrate channel wall coating using a cellulose derivative on a poly‐(methyl methacrylate) (PMMA) CE microchip to eliminate EOF disturbing protein separation. The channel walls were modified by preconditioning with a solution containing the cellulose derivative and then thermally evaporating the solution to produce hydrophilic channel walls which prevent adsorption of analytes via a hydrophobic interaction. When the PMMA substrate was coated with the cellulose derivative hydroxypropylmethylcellulose (HPMC) 90SH, the water contact angle on the coated substrate was decreased (up to 15°) and EOF was significantly suppressed (up to 4.0×10−6 cm2⋅V–1⋅s–1). Three proteins (20.5, 68.0, and 114.6 kDa) were successfully separated on the 0.15% HPMC 90SH‐coated channel walls with good reproducibility of migration time (RSD <1.75%) and high efficiency (theoretical plate number per meter: 2.62×105).
Floating resistivity detector for microchip electrophoresis
Authors: Tay Elaine Teng Teng , Law Wai Siang , Sim Steven Poh Chuen , Feng Huatao , Zhao Jian Hong , Li Sam Fong Yau
Published: December 2007

A newly developed conductivity detector, the floating resistivity detector (FRD), for microchip electrophoresis was introduced in this work. The detector design permits decoupling of the detection circuit from the high separation voltage without compromising separation efficiency. This greatly simplifies the integration of microchip electrophoresis systems. Its method of detection relies on platinum electrodes being dipped in two buffer‐filled branched detection probe reservoirs on the microchip device. In this way, analytes passing through the detection window will not pass through and subsequently adsorb onto the electrodes, alleviating problems of electrode fouling due to analyte contamination and surface reactions. A customized microchip design was proposed and optimized stepwise for the new FRD system. Each branched detection probe was determined to be 4.50 mm long with a 0.075 mm detection window gap between them. The distance between the detection window and buffer waste reservoir was determined to be 1.50 mm. The optimized microchip design was subsequently used in the analysis of four groups of analytes – inorganic cations, amino acids, aminoglycosides antibiotics, and biomarkers. Based on the preliminary results obtained, the detection limits were in the range of 0.4–0.7 mg/L for the inorganic cations and 1.5–15 mg/L for the amino compounds.
Faster and improved microchip electrophoresis using a capillary bundle
Authors: Sun Yi , Kwok Yien Chian , Nguyen Nam Trung
Published: December 2007

Joule heating generated in CE microchips is known to affect temperature gradient, electrophoretic mobility, diffusion of analytes, and ultimately the efficiency and reproducibility of the separation. One way of reducing the effect of Joule heating is to decrease the cross‐section area of microchannels. Currently, due to the limit of fabrication technique and detection apparatus, the typical dimensions of CE microchannels are in the range of 50–200 μm. In this paper, we propose a novel approach of performing microchip CE in a bundle of extremely narrow channels by using photonic crystal fiber (PCF) as separation column. The PCF was simply encapsulated in a poly(methyl methacrylate) (PMMA) microchannel right after a T‐shaped injector. CE was simultaneously but independently carried out in 54 narrow capillaries, each capillary with diameter of 3.7 μm. The capillary bundle could sustain high electric field strength up to 1000 V/cm due to efficient heat dissipation, thus faster and enhanced separation was attained.
Real‐time monitoring of intracellular calcium dynamic mobilization of a single cardiomyocyte in a microfluidic chip pertaining to drug discovery
Authors: Li Xiujun , Huang Jingbo , Tibbits Glen F , Li Paul C.H.
Published: December 2007

A microfluidic method for real‐time quantitative measurement of cellular response pertaining to drug discovery is reported. This method is capable of multiple‐step liquid delivery for measuring the drug response of a single cardiomyocyte, due to the improved cell retention by a newly designed chip. The chip, which consists of a cell‐retention chamber with a weir structure, was fabricated just by a one‐photomask microfabrication procedure followed by on‐chip etching. This method differs from the conventional method, which uses two‐mask photolithography to fabricate the microchannel (deep etch) and the weir structure (shallow etch). The dimensions of the weir structure have been predicted by a mathematical model, and confirmed by confocal microscopy. Using this microfluidic method, the dynamic [Ca2+]i mobilization in a single cardiomyocyte during its spontaneous contraction was quantified. Furthermore, we measured the cellular response of a cardiomyocyte on (i) a known cardiotonic agent (caffeine), (ii) a cardiotoxic chemotherapeutic drug (daunorubicin), and (iii) an herbal anticancer drug candidate – isoliquiritigenin (IQ) based on the fluorescent calcium measurement. It was found that IQ had produced a less pronounced effect on calcium mobilization of the cardiomyocytes whereas caffeine and daunorubicin had much stronger effects on the cells. These three experiments on cardiomyocytes pertaining to drug discovery were only possible after the improved cell retention provided by the new chip design (MV2) required for multiple‐step real‐time cellular analysis on a microchip, as compared with our old chip design (MV1).
SU‐8 as a structural material for labs‐on‐chips and microelectromechanical systems
Authors: Abgrall Patrick , Conedera Veronique , Camon Henri , Gue Anne‐Marie , Nguyen Nam‐Trung
Published: December 2007

Since its introduction in the nineties, the negative resist SU‐8 has been increasingly used in micro‐ and nanotechnologies. SU‐8 has made the fabrication of high‐aspect ratio structures accessible to labs with no high‐end facilities such as X‐ray lithography systems or deep reactive ion etching systems. These low‐cost techniques have been applied not only in the fabrication of metallic parts or molds, but also in numerous other micromachining processes. Its ease of use has made SU‐8 to be used in many applications, even when high‐aspect ratios are not required. Beyond these pattern transfer applications, SU‐8 has been used directly as a structural material for microelectromechanical systems and microfluidics due to its properties such as its excellent chemical resistance or the low Young modulus. In contrast to conventional resists, which are used temporally, SU‐8 has been used as a permanent building material to fabricate microcomponents such as cantilevers, membranes, and microchannels. SU‐8‐based techniques have led to new low‐temperature processes suitable for the fabrication of a wide range of objects, from the single component to the complete lab‐on‐chip. First, this article aims to review the different techniques and provides guidelines to the use of SU‐8 as a structural material. Second, practical examples from our respective labs are presented.
Microfluidic platform with mass spectrometry detection for the analysis of phosphoproteins
Authors: Dawoud Abdulilah A. , Sarvaiya Hetal A. , Lazar Iulia M.
Published: December 2007

The development of novel and reliable technologies for the analysis of proteins and their post‐translational modifications, in particular, has recently received much attention and interest. The implementation of a fully integrated microfluidic device interfaced with MS detection for the analysis of phosphoproteins is presented in this paper. The microfluidic platform (3′′×1.5′′) comprises two individual sample processing systems: one for performing direct sample infusion and one for performing microfluidic LC separations. Various MS detection strategies, specific for the study of post‐translational modifications, were conducted using α‐casein as a model protein. Neutral loss ion mapping, data‐dependent triple‐play and neutral loss analysis, and in situ dephosphorylation followed by LC separation and MS detection were performed. Consistent results in identifying phosphopeptides with conventional and microfluidic instrumentation have been obtained. Unlike with conventional instrumentation, however, the microfluidic device enabled the completion of each analysis from only a few microliters of sample, in ∼10–15 min, and on a bioanalytical platform that facilitates multiplexing and disposability, and thus high‐throughput, contamination‐free analysis.
Stability analysis of SDOF real‐time hybrid testing systems with explicit integration algorithms and actuator delay
Authors: Chen Cheng , Ricles James M.
Published: December 2007

Real‐time hybrid testing is a method that combines experimental substructure(s) representing component(s) of a structure with a numerical model of the remaining part of the structure. These substructures are combined with the integration algorithm for the test and the servo‐hydraulic actuator to form the real‐time hybrid testing system. The inherent dynamics of the servo‐hydraulic actuator used in real‐time hybrid testing will give rise to a time delay, which may result in a degradation of accuracy of the test, and possibly render the system to become unstable. To acquire a better understanding of the stability of a real‐time hybrid test with actuator delay, a stability analysis procedure for single‐degree‐of‐freedom structures is presented that includes both the actuator delay and an explicit integration algorithm. The actuator delay is modeled by a discrete transfer function and combined with a discrete transfer function representing the integration algorithm to form a closed‐loop transfer function for the real‐time hybrid testing system. The stability of the system is investigated by examining the poles of the closed‐loop transfer function. The effect of actuator delay on the stability of a real‐time hybrid test is shown to be dependent on the structural parameters as well as the form of the integration algorithm. The stability analysis results can have a significant difference compared with the solution from the delay differential equation, thereby illustrating the need to include the integration algorithm in the stability analysis of a real‐time hybrid testing system. Copyright © 2007 John Wiley & Sons, Ltd.
Genomic gains of COL1A1‐PDFGB occur in the histologic evolution of giant cell fibroblastoma into dermatofibrosarcoma protuberans
Authors: Macarenco Ricardo S. , Zamolyi Renata , Franco Marcello F. , Nascimento Antonio G. , Abott Jared J. , Wang Xiaoke , Erickson‐Johnson Michele R. , Oliveira Andre M.
Published: December 2007

Giant cell fibroblastoma (GCF) is a subcutaneous mesenchymal neoplasm characterized by the chromosomal t(17;22), which results in the formation of the fusion gene COL1A1‐PDGFB. This same fusion gene is also seen in the supernumerary ring chromosome of dermatofibrosarcoma protuberans (DFSP). Several studies have addressed the molecular genetics of DFSP but molecular cytogenetic characterization of individual areas and cell components in pure GCF and GCF/DFSP hybrids have not been performed. Herein, we studied the frequency and genomic copy number of COL1A1‐PDGFB in pure GCF and GCF/DFSP hybrids, and identified the molecular cytogenetic signatures in individual cells in each component. Four pure GCF and nine GCF/DFSP hybrids were studied. All tumors exhibited classical histological features and CD34 expression. COL1A1 and PDGFB rearrangements were evaluated by fluorescence in situ hybridization (FISH) using probes for COL1A1 and PDGFB on paraffin‐embedded thin tissue sections. All GCF and GCF/DFSP hybrids showed unbalanced rearrangements of COL1A1‐PDGFB at the molecular cytogenetic level. Genomic gains of COL1A1‐PDGFB were found predominantly in the DFSP component of GCF/DFSP hybrids but in none of the pure GCF, suggesting that these gains are associated with the histologic evolution of GCF into DFSP. The molecular cytogenetic abnormalities were found not only in the spindle/stellated cells but also in individual nuclei of the multinucleated giant cells, suggesting that these cells may result from the fusion of individual neoplastic cells. © 2007 Wiley‐Liss, Inc.
Myelin‐phagocytosing macrophages in isolated sciatic and optic nerves reveal a unique reactive phenotype
Authors: van Rossum Denise , Hilbert Sören , Straßenburg Silke , Hanisch Uwe‐karsten , Brück Wolfgang
Published: December 2007

Macrophages are key effectors in demyelinating diseases of the central and peripheral nervous system by phagocytosing myelin and releasing immunoregulatory mediators. Here, we report on a distinct, a priori anti‐inflammatory reaction of macrophages phagocytosing myelin upon contact with damaged nerve tissue. Macrophages rapidly invaded peripheral (sciatic) and central (optic) nerve tissues in vitro, readily incorporated myelin and expressed high levels of phagocytosis‐associated molecules (e.g., Fc and scavenger receptors). In contrast, factors involved in antigen presentation (MHC class‐II, CD80, CD86) revealed only a restricted expression. In parallel, a highly ordered appearance of cytokines and chemokines was detected. IL‐10, IL‐6, CCL22, and CXCL1 were immediately but transiently induced, whereas CCL2, CCL11, and TGFβ revealed more persisting levels. Such a profile would attract neutrophils, monocytes/macrophages, and Th2 cells as well as bias for a Th2‐supporting environment. Importantly, proinflammatory/Th1‐supporting factors, such as TNFα, IL‐12p70, CCL3, and CCL5, were not induced. Still the simultaneous presence of TGFβ and IL‐6 could assist Th17 development, further depending on yet not present IL‐23. The release pattern was clearly distinct from reactive phenotypes induced in isolated macrophages and microglia upon treatment with IL‐4, IL‐13, bacterial lipopolysaccharide, IFNγ, or purified myelin. Nerve‐exposed macrophages thus commit to a unique functional orientation. © 2007 Wiley‐Liss, Inc.
The significance of dyslexia screening for the assessment of dementia in older people
Authors: Metzler‐Baddeley Claudia , Salter Amanda , Jones Roy W.
Published: December 2007

Dyslexia and Dementia are disorders that share cognitive impairments in attention, language, and working memory. It is therefore possible that the presence of dyslexia may influence the assessment of the severity of dementia and potentially lead to the development of atypical forms of dementia. The present study investigated the prevalence of problems suggestive of dyslexia with a brief self‐report questionnaire in a sample of 195 older adults referred to a Memory Clinic for dementia assessment. Ten percent reported problems suggestive of dyslexia consistent with the estimated prevalence in the general population. This group performed significantly lower in a number of attention and language related tests but not in other cognitive domains. These results highlight the importance of dyslexia screening for the assessment of dementia, not least because the choice of treatment is guided by the outcome of the assessment of the severity and the type of dementia. Copyright © 2007 John Wiley & Sons, Ltd.
Abnormal diffusion of cerebral white matter in early blindness
Authors: Shu Ni , Li Jun , Li Kuncheng , Yu Chunshui , Jiang Tianzi
Published: December 2007

Early visual deprivation may lead to both abnormal and plastic changes in the visual and other systems of the brain. Such secondary changes in the gray matter of the early blind have been well studied, but not so well in the cerebral white matter whose subtle changes may be revealed by diffusion tensor imaging. The first purpose of this study is to explore the possible changed white matter regions of the early blind in whole brain manners, using voxel‐based analysis (VBA) and tract‐based spatial statistics (TBSS) methods. The second purpose is to investigate the changes of diffusion eigenvalues in the abnormal white matter fiber tracts using tractography based group mapping analysis. From VBA of fractional anisotropy (FA) images, the significant changed white matter regions were the geniculocalcarine tract (GCT) and its adjacent regions. This finding was validated by TBSS method. Then we studied the changes of mean diffusivity (MD), FA, primary (λ1) and transverse diffusivities (λ23) in the GCT using tractography based group mapping analysis. We found the early blind had significantly lower FA (P < 0.0001), higher MD (P = 0.001) and λ23 (P < 0.0001) in the GCT. This pattern of diffusion changes is similar to findings seen in immaturity or axonal degeneration. Thus, we suggest that transneuronal degeneration and/or immaturity may account for the abnormal diffusion changes in the GCT of the early blind. Hum Brain Mapp 2009. © 2007 Wiley‐Liss, Inc.
MC1R variants associated susceptibility to basal cell carcinoma of skin: Interaction with host factors and XRCC3 polymorphism
Authors: Scherer Dominique , Bermejo Justo Lorenzo , Rudnai Peter , Gurzau Eugene , Koppova Kvetoslava , Hemminki Kari , Kumar Rajiv
Published: December 2007

The variants within the human melanocortin 1 receptor (MC1R) gene are associated with an increased risk of different skin cancers. In this study, we genotyped by direct sequencing, 529 cases of basal cell carcinoma of the skin (BCC) and 533 healthy controls for polymorphisms in the entire MC1R gene. In addition to 10 common polymorphisms, we detected 23 rare variants in the gene. The presence of any nonsynonymous MC1R variant was associated with an increased risk in the carriers (odds ratio OR 1.66, 95% confidence interval CI 1.28–2.14) corresponding to a population attributable fraction of about 27%. The odds ratio for the risk in the carriers of 2 MC1R variants was 2.69 (95% CI 1.77–4.08). The risk of BCC in the carriers of MC1R variants with fair complexion was almost twice as much as in the corresponding noncarriers. The carriers of the R163Q variant with a medium skin complexion were at a 3‐fold higher risk than the noncarrier counterparts. The interaction, of effect on the BCC risk, between the MC1R variants and types of skin response to sun exposure was greater than multiplicative. We also observed a multiplicative interaction of risk due to the MC1R variants and the common allele (high risk) of the T241M polymorphism in the XRCC3 gene. Our data confirmed the status of the nonsynonymous MC1R variants as independent genetic risk factors for BCC. However, the mechanism through which the variants influence the risk likely involves complex interactions with other genetic and host risk factors. © 2007 Wiley‐Liss, Inc.
Regulatory roles of tumor‐suppressor proteins and noncoding RNA in cancer and normal cell functions
Authors: Garen Alan , Song Xu
Published: December 2007

We describe a mechanism for reversible regulation of gene transcription, mediated by a family of tumor‐suppressor proteins (TSP) containing a DNA‐binding domain (DBD) that binds to a gene and represses transcription, and RNA‐binding domains (RBDs) that bind RNA, usually a noncoding RNA (ncRNA), forming a TSP/RNA complex that releases the TSP from a gene and reverses repression. This mechanism appears to be involved in the regulation of embryogenesis, oncogenesis, and steroidogenesis. Embryonic cells express high levels of RNA that bind to a TSP and prevent repression of proto‐oncogenes that drive cell proliferation. The level of the RNA subsequently decreases in most differentiating cells, enabling a TSP to repress proto‐oncogenes and stop cell proliferation. Oncogenesis can result when the level of the RNA fails to decrease in a proliferating cell or increases in a differentiated cell. This mechanism also regulates transcription of P450scc, the first gene in the steroidogenic pathway. © 2007 Wiley‐Liss, Inc.
Determining the drainable pore space through field tests in Konya plain, Turkey
Authors: Bahçeci İdris
Published: December 2007

Drainable pore space (µ) is known as one of the main criteria when designing subsurface drainage systems under unsteady‐state flow conditions. Determining µ is both a difficult and time‐consuming process. An easy and exact method for determining µ could provide researchers with a considerably valuable advantage in decision‐making stages. This parameter is influenced by the soil moisture condition at a certain position and time. When groundwater tables are relatively shallow, the parameter value is highly variable in time and space. Because of this, one should be cautious when using this parameter to design subsurface drainage systems. This paper describes a field experiment to determine the drainable pore space as a function of groundwater table depth and drain discharge and some hydraulic parameters of soil to verify our point of view. Copyright © 2007 John Wiley & Sons, Ltd.
Vascularization and biocompatibility of scaffolds consisting of different calcium phosphate compounds
Authors: Rücker Martin , Laschke Matthias W. , Junker Dominic , Carvalho Carlos , Tavassol Frank , Mülhaupt Rolf , Gellrich Nils‐Claudius , Menger Michael D.
Published: December 2007

Scaffolds for tissue engineering of bone should mimic bone matrix and promote vascular ingrowth. Whether synthetic hydroxyapatite and acellular dentin, both materials composed from calcium phosphate, fulfill these material properties has not been studied yet. Therefore, we herein studied in vivo the host angiogenic and inflammatory response to these biomaterials. Porous scaffolds of hydroxyapatite and isogeneic acellular dentin were implanted into the dorsal skinfold chamber of balb/c mice. Additional animals received perforated implants of isogeneic calvarial bone displaying pores similar in size and structure to those of both scaffolds. Chambers of animals without implants served as controls. Angiogenesis and neovascularization as well as inflammatory leukocyte‐endothelial cell interaction and microvascular leakage were analyzed over a 14‐day time period using intravital fluorescence microscopy. Implantation of both hydroxyapatite and dentin scaffolds showed a slight increase in leukocyte recruitment compared with controls. This was associated with an elevation of microvascular permeability, which was comparable to that observed in response to isogeneic bone. In addition, hydroxyapatite as well as dentin scaffolds induced a marked angiogenic response, which resulted in complete vascularization of the implants until day 14. Of interest, in hydroxyapatite scaffolds, the newly formed capillaries were not as densely meshed as in dentin scaffolds, in which the functional capillary density was comparable to that measured in bone implants. Hydroxyapatite and, in particular, dentin scaffolds promote vascularization and exhibit a biocompatibility comparable to that of isogeneic bone. This may guarantee the rapid incorporation of these materials into the host tissue. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Magnetic nanoparticles for improving cell invasion in tissue engineering
Authors: Sasaki Takuro , Iwasaki Norimasa , Kohno Kenji , Kishimoto Mikio , Majima Tokifumi , Nishimura Shin‐Ichiro , Minami Akio
Published: December 2007

It has been widely recognized that cells are seeded onto only the superficial layer of three‐dimensional (3D) scaffolds in tissue engineering technology. This leads to tissue necrosis that occurs in the central part of 3D scaffolds. To solve this issue, an effective cell seeding technique into the central part of 3D scaffolds is required. Chitosan has characteristics of biocompatibility, biodegradability, and low‐toxicity. In this study, we developed novel magnetic nanoparticles (MNs) coated with chitosan for enhancing cellular invasion using magnetic force. Cell‐invasion efficiency was enhanced by introducing our novel MNs into cells and by the presence of magnetic force. This invasion efficacy depends on the degree of magnetic force. Matrix metalloproteinases and adhesion molecules that were upregulated in response to the attached nanoparticles and exposure to a magnetic force may also play a crucial role in improving cell‐invasive ability in this system. This current system can efficiently enhance cell seeding into the depth of the scaffold, increase subsequent cell–cell interactions and shorten the period of cell proliferation. This system is thought to be useful in the development of cell‐based strategies for the repair or replacement of tissue and other novel therapies. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2008
Functional characterization of P2Y1 versus P2X receptors in RBA‐2 astrocytes: Elucidate the roles of ATP release and protein kinase C
Authors: Weng Ju‐Yun , Hsu Tsan‐Ting , Sun Synthia H.
Published: December 2007

A physiological concentration of extracellular ATP stimulated biphasic Ca2+ signal, and the Ca2+ transient was decreased and the Ca2+ sustain was eliminated immediately after removal of ATP and Ca2+ in RBA‐2 astrocytes. Reintroduction of Ca2+ induced Ca2+ sustain. Stimulation of P2Y1 receptors with 2‐methylthioadenosine 5′‐diphosphate (2MeSADP) also induced a biphasic Ca2+ signaling and the Ca2+ sustains were eliminated using Ca2+‐free buffer. The 2MeSADP‐mediated biphasic Ca2+ signals were inhibited by phospholipase C (PLC) inhibitor U73122, and completely blocked by P2Y1 selective antagonist MRS2179 and protein kinase C (PKC) activator phorbol 12‐myristate 13‐acetate (PMA) whereas enhanced by PKC inhibitors GF109203X and Go6979. Inhibition of capacitative Ca2+ entry (CCE) decreased the Ca2+‐induced Ca2+ entry; nevertheless, ATP further enhanced the Ca2+‐induced Ca2+ entry in the intracellular Ca2+ store‐emptied and CCE‐inhibited cells indicating that ATP stimulated Ca2+ entry via CCE and ionotropic P2X receptors. Furthermore, the 2MeSADP‐induced Ca2+ sustain was eliminated by apyrase but potentiated by P2X4 allosteric effector ivermectin (IVM). The agonist ADPβS stimulated a lesser P2Y1‐mediated Ca2+ signal and caused a two‐fold increase in ATP release but that were not affected by IVM whereas inhibited by PMA, PLC inhibitor ET‐18‐OCH3 and phospholipase D (PLD) inhibitor D609, and enhanced by removal of intra‐ or extracellular Ca2+. Taken together, the P2Y1‐mediated Ca2+ sustain was at least in part via P2X receptors activated by the P2Y1‐induced ATP release, and PKC played a pivotal role in desensitization of P2Y1 receptors in RBA‐2 astrocytes. J. Cell. Biochem. 104: 554–567, 2008. © 2007 Wiley‐Liss, Inc.
Carbon nanotube, graphene, nanowire, and molecule‐based electron and spin transport phenomena using the nonequilibrium Green's function method at the level of first principles theory
Authors: Kim Woo Youn , Kim Kwang S.
Published: December 2007

Based on density functional theory, we have developed a program code to investigate the electron transport characteristics for a variety of nanometer scaled devices in the presence of an external bias voltage. We employed basis sets comprised of linear combinations of numerical type atomic orbitals, particularly focusing on k‐point sampling for the realistic modeling of the bulk electrode. The scheme coupled with the matrix version of the nonequilibrium Green's function method enables calculation of the transmission coefficients at a given energy and voltage in a self‐consistent manner as well as the corresponding current‐voltage (I‐V) characteristics. This scheme has advantages because it is applicable to large systems, easily transportable to different types of quantum chemistry packages, and extendable to time‐dependent phenomena or inelastic scatterings. It has been applied to diverse types of practical electronic devices such as carbon nanotubes, graphene nanoribbons, metallic nanowires, and molecular electronic devices. The quantum conductance phenomena for systems involving quantum point contacts and I‐V curves for a single molecule in contact with metal electrodes using the k‐point sampling method are described. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
DFT conformational studies of α‐maltotriose
Authors: Schnupf Udo , Willett Julious L. , Bosma Wayne B. , Momany Frank A.
Published: December 2007

Recent DFT optimization studies on α‐maltose improved our understanding of the preferred conformations of α‐maltose. The present study extends these studies to α‐maltotriose with three α‐D‐glucopyranose residues linked by two α‐[1→4] bridges, denoted herein as DP‐3's. Combinations of gg, gt, and tg hydroxymethyl groups are included for both “c” and “r” hydroxyl rotamers. When the hydroxymethyl groups are for example, gg‐gg‐gg, and the hydroxyl groups are rotated from all clockwise, “c”, to all counterclockwise, “r”, the minimum energy positions of the bridging dihedral angles (ϕH and ψH) move from the region of conformational space of (−, −), relative to (0°, 0°), to a new position defined by (+, +). Further, it was found previously that the relative energies of α‐maltose gg‐gg‐c and “r” conformations were very close to one another; however, the DP‐3's relative energies between hydroxyl “c” or “r” rotamers differ by more than one kcal/mol, in favor of the “c” form, even though the lowest energy DP‐3 conformations have glycosidic dihedral angles similar to those found in the α‐maltose study. Preliminary solvation studies using COSMO, a dielectric solvation method, point to important solvent contributions that reverse the energy profiles, showing an energy preference for the “r” forms. Only structures in which the rings are in the chair conformation are presented here. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
Electron localizability indicators ELI and ELIA: The case of highly correlated wavefunctions for the argon atom
Authors: Bezugly Viktor , Wielgus Pawel , Wagner Frank R. , Kohout Miroslav , Grin Yuri
Published: December 2007

Electron localizability indicators based on the same‐spin electron pair density and the opposite‐spin electron pair density are studied for correlated wavefunctions of the argon atom. Different basis sets and reference spaces are used for the multireference configuration interaction method following the complete active space calculations aiming at the understanding of the effect of local electron correlation when approaching the exact wavefunction. The populations of the three atomic shells of Ar atom in real space are calculated for each case. © 2007 Wiley Periodicals, Inc. J Comput Chem 29: 1198–1207, 2008
Sonography of endometriosis in infrequent sites
Authors: Park Sung Bin , Kim Jeong Kon , Cho Kyoung‐Sik
Published: December 2007

We reviewed the sonographic features of endometriosis in infrequent sites, including the abdominal wall, appendix, perineum, and bladder. Familiarity with the clinical setting and the songraphic appearance of endometriosis in both frequent and infrequent sites can help facilitate prompt, accurate diagnosis and treatment. © 2007 Wiley Periodicals, Inc. J Clin Ultrasound, 2008
Analysis of the intracellular barriers encountered by nonviral gene carriers in a model of spatially controlled delivery to neurons
Authors: Bergen Jamie M. , Pun Suzie H.
Published: December 2007

Background

Neuron‐specific, nonviral gene delivery vehicles are useful tools for the potential treatment of neurological disease and spinal cord injury. For minimally invasive, peripheral administration, gene carriers must efficiently mediate uptake at axon terminals, retrograde axonal transport, vesicular escape, and nuclear entry. The design of improved vehicles will benefit from an understanding of the barriers that limit nonviral delivery to neurons. Here, we demonstrate a detailed analysis of intracellular trafficking of both a lipid‐based and a polymer‐based delivery vehicle following site‐specific exposure to neuron‐like cells.

Methods

Site‐specific exposure of gene carriers to soma or neurites of neuron‐like PC‐12 cells was accomplished using a microfluidic, compartmented culture chamber. Binding and internalization of vehicles at neurites and soma were quantified using an environmentally sensitive fluorescent marker. The intracellular transport of gene carriers was analyzed by time‐lapse particle tracking in live cells, and transfection efficiencies were measured using green fluorescent protein (GFP) as a reporter gene.

Results

While the lipid‐based carrier mediated measurable transfection when delivered to neuronal soma, neuritic delivery of this formulation failed to produce reporter gene expression due to limited internalization and transport. In contrast, the polymeric nanoparticles displayed active retrograde transport toward neuronal soma, but failed to produce measurable reporter gene expression.

Conclusions

These results highlight distinct intracellular barriers preventing efficient neuronal transfection by the nonviral carriers examined, and provide a basis for the rational improvement of existing nonviral systems. Copyright © 2007 John Wiley & Sons, Ltd.
Highly efficient gene transfer with degradable poly(ester amine) based on poly(ethylene glycol) diacrylate and polyethylenimine in vitro and in vivo
Authors: Park Mi Ran , Kim Hyon Woo , Hwang Chang Sun , Han Ki Ok , Choi Yun Jaie , Song Soo Chang , Cho Myung Haing , Cho Chong Su
Published: December 2007

Background

Polyethylenimine (PEI) is toxic although it is one of the most successful and widely used gene delivery polymers with the aid of the proton sponge effect. Therefore, development of new novel gene delivery carriers having high efficiency with less toxicity is necessary.

Methods

In this study, a degradable poly(ester amine) carrier based on poly(ethylene glycol) diacrylate (PEGDA) and low molecular weight linear PEI was prepared. Furthermore, we compared the gene expression of the polymer/DNA complexes using two delivery methods: intravenous administration as an invasive method and aerosol as a non‐invasive method.

Results

The synthesized polymer had a relatively small molecular weight (MW = 7980) with 25 h half‐life in vitro. The polymer/DNA complexes were formed at an N/P ratio of 9. The particle sizes and zeta‐potentials of the complexes were dependent on N/P ratio. Compared to PEI 25K, the newly synthesized polymer exhibited high transfection efficiency with low toxicity. Poly(ester amine)‐mediated gene expression in the lung and liver was higher than that of the conventional PEI carrier. Interestingly, non‐invasive aerosol delivery induced higher gene expression in all organs compared to intravenous method in an in vivo mice study. Such an expressed gene via a single aerosol administration in the lung and liver remained unchanged for 7 days.

Conclusions

Our study demonstrates that poly(ester amine) may be applied as an useful gene carrier. Copyright © 2007 John Wiley & Sons, Ltd.
Inducing huntingtin inclusion formation in primary neuronal cell culture and in vivo by high‐capacity adenoviral vectors expressing truncated and full‐length huntingtin with polyglutamine expansion
Authors: Huang Bin , Schiefer Johannes , Sass Christian , Kosinski Christoph M. , Kochanek Stefan
Published: December 2007

Background

Huntington's disease (HD) is an inherited autosomal dominant neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat in exon 1 of the huntingtin (htt) gene. Vector‐mediated delivery of N‐terminal fragments of mutant htt has been used to study htt function in vitro and to establish HD models in rats. Due to the large size of the htt cDNA vector‐mediated delivery of full‐length htt has not been achieved so far.

Methods

High‐capacity adenoviral (HC‐Ad) vectors were generated expressing mutant and wild‐type versions of N‐terminal truncated and full‐length htt either in vitro in primary neuronal cells or in the striatum of mice.

Results

In vitro these vectors were used for transduction of primary neuronal cells isolated from E17 mouse embryos. Expression of mutant htt resulted in the formation of htt inclusions, a surrogate marker of the HD pathology. Kinetics of generation and localization of htt inclusions differed between truncated and full‐length htt carrying identical mutations. Following injection into the striatum vector‐mediated expression of mutant truncated htt led to prominent accumulation of htt inclusions in cell nuclei, while inclusions formed upon expression of mutant full‐length htt localized to the cytoplasm.

Conclusions

These results indicate that HC‐Ad vector‐mediated in vitro and in vivo delivery of truncated and full‐length mutant htt results in prominent inclusion formation in neuronal cells but in different cell compartments. These vectors will be useful tools for studying HD and may be used to generate large animal HD models. Copyright © 2007 John Wiley & Sons, Ltd.
The effect of superoxide dismutase deficiency on zinc toxicity in Schizosaccharomyces pombe
Authors: Tarhan Cagatay , Pekmez Murat , Karaer Semian , Arda Nazli , Sarikaya Aysegul T.
Published: December 2007

Zinc is a metal which is a cofactor in many enzymes and a structural element in zinc finger motifs those are important in relation between DNA and regulator proteins. Little is known about uptake, distribution, toxicity and detoxification of zinc ions in cells. In this study, zinc toxicity and detoxification levels have been compared in wild type and Cu/Zn superoxide dismutase mutant (sod1Δ) cells of the fission yeast Schizosaccharomyces pombe. We evaluated the toxic levels of zinc, total zinc content, lipid peroxidation levels and catalase activities for both strains which were grown in medium containing different concentrations of zinc. sod1Δ mutant showed important growth retardation and has higher lipid peroxidation and catalase activities than wild type. Cu/Zn superoxide dismutase (SOD1) activity of wild type cells was markedly increased when they were treated with elevated levels of zinc. SOD1 mRNA level also significantly increased when the cells treated with higher concentrations of zinc. These results indicate that the mutant cells were more sensitive to zinc stress and seemed to have more oxidative intracellular environment than wild type cells. Our results support the idea that superoxide dismutase is an important factor for zinc detoxification in eukaryotes. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Surgical performance of a 405-nm diode laser in treatment of soft tissue
Authors: Kato J , Hatayama H , Miyazaki H , Akashi G , Moriya K , Inoue A , Hirai Y
Published: December 2007

The study was conducted to evaluate the surgical performance of a 405-nm diode laser ex vivo. The experiments were carried out using tuna tissue, which was irradiated with a 405-nm diode laser at output powers of 400 mW (694 W/cm2) to 1 W (1735 W/cm2) on a motorized stage moving at a rate of 1 mm/sec. As a control, a 920-nm diode laser was used with the same irradiation conditions. After irradiation, the thickness of ablation and coagulation was measured by stereoscopic microscopy and evaluated statistically. Ablation and coagulation zones were obtained with 405-nm laser irradiation, but not with irradiation at 920 nm. Ablation depth increased significantly with output power and a thick coagulation zone was observed with 405-nm irradiation. The 405-nm diode laser performed well for incising and coagulating soft tissue at a low power density.
Loading and in vitro Controlled Release of Indomethacin Using Amphiphilic Cholesteryl‐Bearing Carboxymethylcellulose Derivatives
Authors: Yang Liqun , Kuang Jianliang , Wang Jun , Li Zhiquan , Zhang Li‐Ming
Published: December 2007

Amphiphilic CCMCs were synthesized under mild conditions and their chemical structures were characterized by FT‐IR and 1H NMR spectroscopy. Fluorescence analysis showed that CCMCs could self‐associate to form polymeric micelles in aqueous solution. IND was encapsulated during the formation of CCMC micelles and its in vitro release properties were investigated. The loading capacity was more than 50% and the loaded IND was slowly and steadily released into the medium over a period of 8 h. The CCMC micelles showed pH‐responsive behavior during the drug‐loading and release processes. CCMC is promising as a potential delivery system for the controlled release of IND with a pH‐responsive property.

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Application of a multi‐channel zero‐resistance current amplifier for screening processes
Authors: Plagemann P. , Anton A. , Yezerska O. , Schneider M. , Schrems P.
Published: December 2007

In addition to being a very useful monitoring technique, electrochemical noise analysis is also particularly suitable for screening purposes. A multi‐channel zero‐resistance current amplifier was designed in order to be able to carry out multiple noise measurements simultaneously, thus allowing a greater number of tests to be performed in a given time. Electrochemical noise measurements were carried out on AA 2024 in NaCl solutions of different concentrations and in the presence of inhibitors to highlight the practical relevance of this analytical method. The results show that the noise data can be evaluated in a simple and clear way using the noise charge.