bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Structure of the Chloroiron(III) Derivative of the meso‐Unsubstituted 2,7,12,17‐Tetramethyl‐3,8,13,18‐tetramesitylporphyrin and Weak Ferromagnetic Exchange Interactions in the A1u Oxoiron(IV) Porphyrin π Radical Cation Complex
Authors: Ayougou Khadija , Mandon Dominique , Fischer Jean , Weiss Raymond , Müther Markus , Schünemann Volker , Trautwein Alfred X. , Bill Eckhard , Terner James , Jayaraj Karupiah , Gold A. , Austin Rachel N.
Published: September 2007

The molecular structure of the chloroiron(III) porphyrinate [FeIIICl‐ (tmtmp)] (1) is described. The doming off the bifacially encumbered tmtmp dianionic ligand present in 1 is characterized by a separation of 0.09 (1) Å between the mean plane of the four pyrrole nitrogens (4NP) and that of the porphyrin core. The coordination polyhedron of the five‐coordinate iron atom is a square pyramid of C4v symmetry. The metal is displaced by 0.44 (1) Å from the 4Np mean plane towards the axial chloro ligand. The Fe–Np and Fe‐Cl bond lengths are 2.057 (6) and 2.223(5) Å, respectively. Upon treatment of [FeIIITf(tmtmp)] (2) with m‐chloroperoxybenzoic acid, the green oxoferryl π radical cation complex [FeIV=O(tmtmp)]+ (3) is obtained. It has been studied by EPR, Mössbauer, and resonance Raman spectroscopy. It exhibits an EPR spectrum strikingly similar to those of compounds I of Micrococcus lysodeikticus catalase (APX‐I) and ascorbate peroxidase (APX‐I) The exchange interactions between the spins of the radical cation and the ferryl iron are of the ferromagnetic type and are the weakest ever found for a synthetic compound I model. The shift of + 22 cm‐1 in the radical marker band v2 in the resonance Raman spectra upon oxidation of 2 to 3 confirms that the electronic state of the porphyrin π radical cation is predominantly 2Alu in this tmtmp compound 1 model.
Homochiral and Heterochiral Dimers of the Methylzinc Alkoxide Formed from Dimethylzinc and Enantiomeric 3‐exo‐(Dimethylamino)isoborneol—Origin of the Distinct Differences in Solution‐Phase Behavior and Crystal Structures
Authors: Kitamura Masato , Yamakawa Masashi , Oka Hiromasa , Suga Seiji , Noyori Ryoji
Published: September 2007

Dimethylzinc reacts with (2S)‐or (2R)‐3‐exo‐(dimethylamino)isoborneol [(2S)‐ or (2R)‐DAIB] to eliminate methane and produce a tricoordinate methylzinc aminoalkoxide, which forms a dimeric structure. The homochiral dimerization of the enantiomeric compound leads to the chiral, (S,S) or (R,R) dinuclear Zn complex, while the heterochiral interaction forms the meso (S,R) dinuclear compound. In both solution and crystalline state, the heterochiral dimer is more stable than the homochiral dimer. This stability difference in solution is the origin of the chirality amplification observed in the amino alcohol promoted asymmetric addition of dimethylzinc to benzaldehyde. In toluene, the homochiral dimer dissociates more readily into the monomer than the heterchiral isomer and also undergoes dissociation of the N‐Zn dative bond making the two N‐methyl groups equivalent. The differences in solution behavior between the diastereomers can be understood by comparing their crystal structures. X‐ray analysis indicates that the labile Zn‐O and Zn‐N bonds in the (S,S) dimer are longer than those in the (S,R) isomer. Skeletal congestion caused by the polycyclic framework is the prime factor determining the properties of the dinuclear Zn complexes, with both steric and electronic factors governing their geometries. The distances between the C‐2 proton and N‐CH3 of the other DAIB moiety in the homochiral dimer are close to the sum of the van der Waals radii. A significant nuclear Overhauser effect is seen between these protons in the homochiral dimer. The tetrahedral Zn atoms in the dinuclear complexes are linked covalently to the methyl group, to two oxygen atoms through covalent/electrostatic hybrid bonds, and to the dimethylamino group through electrostatic interaction. The repulsive interaction of the 1, 3‐synoriented Zn‐CH3 bonds significantly contributes to the lower stability of the homochiral dimeric complex. The N‐Zn interaction in the homochiral dimer is labile, owing to the increase in the electrostatic interaction between the Zn atom and the neighboring oxygen atoms. This view is supported by the ab initio molecular orbital calculations of the model systems.
Predictive and prognostic value of FDG‐PET in nonsmall‐cell lung cancer
Authors: de Geus‐Oei Lioe‐Fee , van der Heijden Henricus F.M. , Corstens Frans H.M. , Oyen Wim J.G.
Published: September 2007

For several years, molecular imaging with 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) has become part of the standard of care in presurgical staging of patients with nonsmall‐cell lung cancer (NSCLC), focusing on the detection of malignant lesions at early stages, early detection of recurrence, and metastatic spread. Currently, there is an increasing interest in the role of FDG‐PET beyond staging, such as the evaluation of biological characteristics of the tumor and prediction of prognosis in the context of treatment stratification and the early assessment of tumor response to therapy. In this systematic review, the literature on the value of the evolving applications of FDG‐PET as a marker for prediction (ie, therapy response monitoring) and prognosis in NSCLC is addressed, divided in sections on the predictive value of FDG‐PET in locally advanced and advanced disease, the prognostic value of FDG‐PET at diagnosis, after induction treatment, and in recurrent disease. Furthermore, the background and recommendations for the application of FDG‐PET for these indications will be discussed. Cancer 2007. © 2007 American Cancer Society.
Similarities and differences of human and experimental mouse lymphangiomas
Authors: Kasten Philipp , Schnöink Gerrit , Bergmann Astrid , Papoutsi Maria , Buttler Kerstin , Rössler Jochen , Weich Herbert A. , Wilting Jörg
Published: September 2007

Lymphangioma is a disfiguring malformation of early childhood. A mouse lymphangioma model has been established by injecting Freund's incomplete adjuvant (FIA) intraperitoneally, but has not been compared with the human disease. We show that, in accordance with studies from the 1960s, the mouse model represents an oil‐granuloma, made up of CD45‐positive leukocytes and invaded by blood and lymph vessels. Several markers of lymphatic endothelial cells are expressed in both mouse and human, like CD31, Prox1, podoplanin, and Lyve‐1. However, the human disease affects all parts of the lymphovascular tree. We observed convolutes of lymphatic capillaries, irregularly formed collectors with signs of disintegration, and large lymph cysts. We observed VEGFR‐2 and ‐3 expression in both blood vessels and lymphatics of the patients, whereas in mouse VEGFR‐2 was confined to activated blood vessels. The experimental mouse FIA model represents a vascularized oil‐granuloma rather than a lymphangioma and reflects the complexity of human lymphangioma only partially. Developmental Dynamics 236:2952–2961, 2007. © 2007 Wiley‐Liss, Inc.
Homeobox gene Sax2 deficiency causes an imbalance in energy homeostasis
Authors: Simon Ruth , Lufkin Thomas , Bergemann Andrew D.
Published: September 2007

The brain, in particular the hypothalamus and the brainstem, plays a critical role in the regulation of energy homeostasis by incorporating signals from the periphery and translating them into feeding behavior. Here we show that the homeobox gene Sax2, which is expressed predominantly in the brainstem, in the vicinity of serotonergic neurons, contributes to this physiological balance. Sax2 deficiency results in a decrease of fat and glycogen storage, reduced blood glucose levels, and raised serotonin levels in the hindbrain. Surprisingly, in the brainstem the expression levels of pro‐opiomelanocortin and neuropeptide Y were indicative of a fasting condition, opposed to the observed high serotonin levels implying satiation. Furthermore, Sax2‐directed lacZ expression reveals a dramatic change of the distribution of Sax2‐expressing cells in the null mutant occurring during perinatal development. These data strongly suggest that Sax2 is required for the coordinated crosstalk of factors involved in the maintenance of energy homeostasis. Developmental Dynamics 236:2792–2799, 2007. © 2007 Wiley‐Liss, Inc.
A flk‐1 promoter/enhancer reporter transgenic Xenopus laevis generated using the Sleeping Beauty transposon system: An in vivo model for vascular studies
Authors: Doherty Joanne R. , Johnson Hamlet Michelle R. , Kuliyev Emin , Mead Paul E.
Published: September 2007

We have used the Sleeping Beauty (SB) transposable element to generate transgenic Xenopus laevis with expression of green fluorescent protein (GFP) in vascular endothelial cells using the frog flk‐1 promoter. This is the first characterization of a SB‐generated transgenic Xenopus that has tissue‐restricted expression. We demonstrate that the transgene integrated into single genomic loci in two independent founder lines and is transmitted through the germline at the expected Mendelian frequencies. Transgene integration occurred through a noncanonical transposition process possibly reflecting Xenopus‐specific interactions with the SB system. The transgenic animals express GFP in the same spatial and temporal pattern as the endogenous flk‐1 gene throughout development and into adulthood. Overexpression of xVEGF122 in the transgenic animals disrupts vascular development that is visualized by fluorescent microscopy. These studies demonstrate the convenience of the SB system for generating transgenic animals and the utility of the xflk‐1:GFP transgenic line for in vivo studies of vascular development. Developmental Dynamics 236:2808–2817, 2007. © 2007 Wiley‐Liss, Inc.
Numerical characteristics of peer‐to‐peer (P2P) internet online hybrid test system and its application to seismic simulation of SRC structure
Authors: Wang Tao , Yoshitake Nobuya , Pan Peng , Lee Tae‐Hyung , Nakashima Masayoshi
Published: September 2007

The peer‐to‐peer (P2P) Internet online hybrid test system has been developed for the seismic simulation of a structure. In this study, the stability and accuracy of the system are investigated analytically by studying the spectral radius of the recursive matrix of the test scheme featuring a two‐round quasi‐Newton test scheme. The applicability of the system is further examined by exploring the seismic responses of a complex structure, a steel‐encased reinforced concrete (SRC) structure with a steel tower on the top. The structure is divided into two numerical substructures and one tested part for hybrid test. The numerical substructures are simulated by sophisticated finite element method (FEM) models with material nonlinearities to capture local plastifications. Two types of FEM programs, namely OpenSEES and ABAQUS, which are suitable for the SRC part and the steel tower, respectively, are employed. The results demonstrate that the P2P system is able to simulate complex structures with significant nonlinearities. As compared with the previous study in which two elastic numerical substructures were considered, increase in the number of iterations in this study is not significant, because the associated nonlinearities are limited due to the small time interval adopted in the test. Copyright © 2007 John Wiley & Sons, Ltd.
Generation of fragility curves for Turkish masonry buildings considering in‐plane failure modes
Authors: Erberik M. Altuğ
Published: September 2007

This study focuses on the seismic safety evaluation of masonry buildings in Turkey for in‐plane failure modes using fragility curves. Masonry buildings are classified and a set of fragility curves are generated for each class. The major structural parameters in the classification of masonry buildings are considered as the number of stories, load‐bearing wall material, regularity in plan and the arrangement of walls (required length, openings in walls, etc.), in accordance with the observations from previous earthquakes and field databases. The fragility curves are generated by using time history (for demand) and pushover (for capacity) analyses. From the generated sets of fragility curves, it is observed that the damage state probabilities are significantly influenced from the number of stories and wall material strength. In the second stage of the study, the generated fragility curves are employed to estimate the damage of masonry buildings in Dinar after the 1995 earthquake. The estimated damage by fragility information is compared with the inspected
visual damage as assessed from the Damage Evaluation Form. For the quantification of fragility‐based damage, a single‐valued index, named as ‘vulnerability score’ (VS), is proposed. There seems to be a fair agreement between the two damage measures. In addition to this, decisions regarding the repair or demolition of masonry buildings in Dinar due to visual damage inspection are on comparable grounds with the relative measure obtained from VS of the same buildings. Hence, the fragility‐based procedure can provide an alternative for the seismic safety evaluation of masonry buildings in Turkey. Copyright © 2007 John Wiley & Sons, Ltd.
A multilevel domain decomposition approach to solving coupled applications in computational fluid dynamics
Authors: Aulisa Eugenio , Manservisi Sandro , Seshaiyer Padmanabhan
Published: September 2007

Direct numerical simulation of the non‐linear equations, governing a fluid–structure system, relies heavily on the properties of the coupled system and the corresponding iterative solver. The purpose of this paper is to introduce a flexible and robust multilevel finite element algorithm that can be used to study the behavior of a fully coupled fluid–structure system. The method relies on the domain decomposition characteristics of the multigrid Vanka solvers, which decompose the complex global domain into the finite element local sub‐domains and then compute the global solution iteratively. This particular methodology allows us to solve easily this coupled system over a fluid–solid domain which consists of a set of subdomains from different mesh levels with conforming or non‐conforming finite element method approximations. The multigrid projection and restriction operators are used to impose the matching between the extended fluid and solid velocity field. Copyright © 2007 John Wiley & Sons, Ltd.
Improvements in speed for explicit, transient compressible flow solvers
Authors: Löhner Rainald , Luo Hong , Baum Joseph D. , Rice Darren
Published: September 2007

Several explicit high‐resolution schemes for transient compressible flows with moving shocks are combined in such a way so as to achieve the highest possible speed without compromising accuracy. The main algorithmic changes considered comprise the following:

replacing limiting and approximate Riemann solvers by simpler schemes during the initial stages of Runge–Kutta solvers, and only using limiting and approximate Riemann solvers for the last stage;

automatically switching to simpler schemes for smooth flow regions;

automatic deactivation of quiescent regions; and

unstructured grids with cartesian cores or embedded cartesian grids.

The results from several examples demonstrate that speedup factors of 1:4 are attainable without compromising the accuracy of the traditional FCT schemes. Copyright © 2007 John Wiley & Sons, Ltd.
Simulation of liquid sloshing in curved‐wall containers with arbitrary Lagrangian–Eulerian method
Authors: Zhou H. , Li J. F. , Wang T. S.
Published: September 2007

There are many challenges in the numerical simulation of liquid sloshing in horizontal cylinders and spherical containers using the finite element method of arbitrary Lagrangian–Eulerian (ALE) formulation: tracking the motion of the free surface with the contact points, defining the mesh velocity on the curved wall boundary and updating the computational mesh. In order to keep the contact points slipping along the curved side wall, the shape vector in each time advancement is defined to modify the kinematical boundary conditions on the free surface. A special function is introduced to automatically smooth the nodal velocities on the curved wall boundary based on the liquid nodal velocities. The elliptic partial differential equation with Dirichlet boundary conditions can directly rezone the inner nodal velocities in more than a single freedom. The incremental fractional step method is introduced to solve the finite element liquid equations. The numerical results that stemmed from the algorithm show good agreement with experimental phenomena, which demonstrates that the ALE method provides an efficient computing scheme in moving curved wall boundaries. This method can be extended to 3D cases by improving the technique to compute the shape vector. Copyright © 2007 John Wiley & Sons, Ltd.
A reduced model of the Madden–Julian oscillation
Authors: Wedi Nils P. , Smolarkiewicz Piotr K.
Published: September 2007

We have extended our virtual laboratory for internal wave motions (Int. J. Numer. Meth. Fluids 2005; 47:1369–1374) to the case of rotating fluids on an equatorial β‐plane. A virtual wave‐maker is introduced via a time‐dependent coordinate transformation in the meridional direction, represented by two lateral boundary meanders. The technique is consistently incorporated into the numerical algorithm of the nonhydrostatic model EULAG. The modelling framework is applied in simulations of equatorial wave motions to enhance our understanding of the Madden–Julian oscillation (MJO). The simulation of a realistic MJO in global circulation and climate models is a continuing challenge—in part, due to the failure of existing theories to explain the ubiquitous modelling difficulties of the phenomenon. Virtual laboratory experiments appear ideal complementary tools to isolate and study particular geophysical flow structures. In
these laboratory‐scale ‘climate’ simulations we observe eastward propagating low‐frequency horizontal structures consistent with Rossby solitary wave theory, representing a particular solution of the Korteweg–de Vries equation for the evolution of the wave amplitude under a given forcing. The latter extends the linear shallow water theory—commonly used to explain different modes of equatorial wave motions—to the weakly nonlinear regime. One important outcome of our simulations is the finding that these structures depend on strong stratification, and may be easily destroyed or weakened if substantial near‐surface perturbations and associated vertical motions exist. This could play a role in the failure to simulate a realistic MJO, but it may also provide an explanation why solitary waves are not as readily observed in oceans as they are in models and theory. Ultimately, our research aims at constructing a simplified dynamical apparatus to reproduce MJO‐like structures in a laboratory analogue, in the spirit of the Plumb–McEwan experiment for the quasi‐biennial oscillation and vis‐a‐vis its numerical equivalent. Copyright © 2007 John Wiley & Sons, Ltd.
Studies of Material Interaction After Long‐Term Stack Operation
Authors: Menzler N. H. , Batfalsky P. , Blum L. , Bram M. , Groß S. M. , Haanappel V. A. C. , Malzbender J. , Shemet V. , Steinbrech R. W. , Vinke I.
Published: September 2007

Forschungszentrum Jülich is routinely operating solid oxide fuel cells (SOFCs) in stacks of planar design. Anode‐supported cells are used in combination with ferritic steel interconnects as standard components. The stacks are typically sealed with glass‐ceramics. In order to examine the long‐term interaction between the materials comprising these components, and the contact and protection layers, SOFC stacks with operation times of more than 6,000 h at 800 °C have been disassembled and microstructurally examined. The stack disassembling and examination procedures are outlined and results from optical and scanning electron microscopy are presented. Two interaction observations that are considered to affect stack performance are addressed in detail. The effects refer to the reaction of the glass‐ceramic sealant with the ferritic steel interconnect and to Cr deposition at the cathode/electrolyte interface. Measures and strategies to diminish and/or to prevent unwanted long‐term material interactions are discussed.
Intermolecular Interactions Between Methanol/Water Molecules and Nafion™ Membrane: An Infrared Spectroscopy Study
Authors: Tsai C.‐E. , Hwang B.‐J.
Published: September 2007

The intermolecular interactions between methanol/water and Nafion™ membranes have been investigated using IR spectroscopy. The evolution of IR spectra of the Nafion™ membranes, immersed in various concentrations of methanol solution depends strongly on the methanol concentration. The O–H bending vibration modes at 1,636, 1,660 and 1,672 cm–1 associated with the hydrogen bonding of (H3O+…SO3–) as well as (CH3OH2+…SO3–), and at 1,702, 1,717 and 1,711–1,736 cm–1 associated with the hydrogen bonding of (CF2…H–O–CH3), (CF2…H–OH), (CF2…+H3O) and (CF2…H–OSO2–) were observed. The vibration mode of (CF2…H–O) was found to be appearing obviously at 3,821–3,900 cm–1 when the Nafion™ membrane was immersed in the methanol solution with concentration higher than 6 M. On the other hand, the wavenumber of the O–H stretching peak increases with an increase in the methanol concentration. Results of IR spectra revealed that the methanol molecules show better capability to penetrate into the hydrophobic domain of the Nafion™ membrane than water. The intermolecular interaction between the hydrophobic domains of Nafion™ and methanol molecules becomes more observable at a higher methanol concentration.
Characterisation of Ni–YSZ‐Cermets with Respect to Redox Stability
Authors: Ettler M. , Blaß G. , Menzler N. H.
Published: September 2007

In anode‐supported solid oxide fuel cells (SOFCs), air break‐in on the anode side can result in reoxidation of metallic nickel. The volume expansion caused by Ni oxidation generates stresses within the substrate, the anode and the electrolyte. Those stresses exceed the stability of the components, potentially promoting crack growth. Therefore, either the SOFC degrades continuously after each redox‐cycle or the membrane electrode assembly (MEA) fails completely if the electrolyte cracks.

The influence of several reoxidation parameters on the mechanical integrity of Ni–YSZ‐anodes after reoxidation was investigated using different types of samples. All samples were SFEs (substrate–functional layer–electrolytes), consisting of Ni–YSZ‐substrate, Ni–YSZ‐anode and YSZ‐electrolyte. Investigations were carried out on freestanding SFEs and SFEs attached to steel plates (Crofer22APU, Thyssen Krupp V. D. M., Material Data Sheet No. 4046, Edition of December 2006) with a glass sealing.

The results show a big influence of the degree of oxidation, homogeneity of oxidation, the operating temperature and the incident flow on the behaviour and the mechanical integrity of the reoxidised SFEs. The time of oxidation and the gas flow rate were influencing parameters, whereas the influence of the porosity was insignificant. The behaviour of the SFEs upon reoxidation also changes dramatically when comparing freestanding samples with attached samples.
Dynamic Modelling of a Polymer Electrolyte Membrane Fuel Cell Stack by Nonlinear System Identification
Authors: Buchholz M. , Krebs V.
Published: September 2007

Real‐time models of polymer electrolyte membrane fuel cell (PEMFC) stacks with high accuracy are required, e.g. for the design of controllers or online diagnosis tools. By using physical and chemical laws representing the processes in a PEMFC stack, very detailed, but computationally complex models can be retrieved.

In this paper, a nonlinear dynamic model obtained by system identification is proposed for PEMFC stacks. The model structure in this contribution is based on a modular concept and is divided into a static and a dynamic part. The static part represents the stationary points and the dynamic part describes the deviation from these stationary points due to changes in the input signals. Both parts can be modelled by different methods. A characteristic map and a neural network (NN) are proposed for the static part. For the dynamic part, transfer functions and a linear state‐space model retrieved by canonical variate analysis (CVA) are investigated.
Mutations in the ataxia telangiectasia and rad3‐related–checkpoint kinase 1 DNA damage response axis in colon cancers
Authors: Lewis Kriste A. , Bakkum‐Gamez Jamie , Loewen Ralitsa , French Amy J. , Thibodeau Stephen N. , Cliby William A.
Published: September 2007

In response to certain types of DNA damage, ataxia telangiectasia and rad3‐related (ATR) phosphorylates checkpoint kinase 1 (CHEK1) resulting in cell cycle arrest and subsequent DNA repair. ATR and CHEK1 contain mononucleotide microsatellite repeat regions, which are mutational targets in tumors with defective mismatch repair (MMR). This study examined the frequency of such mutations in colon cancers and their impact on biologic behavior. Screening for ATR mutations in 48 tumors was performed using denaturing high‐performance liquid chromatography (DHPLC) and confirmed with sequencing analysis. The CHEK1 exon 7 A(9) region was sequenced in 20 of the 27 (74%) tumors with high frequency of microsatellite instability (MSI‐H). Univariate and multivariate analyses were used to examine associations with clinical outcomes. Frequent mutations in MSI‐H colon cancers were identified within the ATR (37%)/CHEK1(5%) damage response pathway. Stage and MSI status both independently predicted overall survival (OS) and disease‐free survival (DFS). ATR status was not associated with stage, but was associated with a trend toward improved DFS: 0/9 cancers recurred in MSI‐H cases harboring ATR mutations vs. 4/18 recurrences in MSI‐H cases without ATR mutations. This suggests that ATR mutations may affect clinical behavior and response to therapy in MSI‐H colon cancers. © 2007 Wiley‐Liss, Inc.
Effects of exercise on NMDA receptor subunit contributions to bidirectional synaptic plasticity in the mouse dentate gyrus
Authors: Vasuta Cristina , Caunt Charlotte , James Rachel , Samadi Shervin , Schibuk Elizabeth , Kannangara Timal , Titterness Andrea K. , Christie Brian R.
Published: September 2007

We examined synaptic plasticity in the dentate gyrus (DG) of the hippocampus in vitro in juvenile C57Bl6 mice (28–40 days of age), housed in control conditions with minimal enrichment (Controls) or with access to an exercise wheel (Runners). LTP expression was significantly greater in slices from Runners than in those from Controls, but could be blocked by APV in both groups. LTP was significantly reduced by NR2B subunit antagonists in both groups. NVP‐AAM077, an antagonist with a higher preference for NR2A subunits over NR2B subunits, blocked LTP in slices from Runners and produced a slight depression in Control animals. LTD in the DG was also blocked by APV, but not by either of the NR2B specific antagonists. Strikingly, NVP‐AAM077 prevented LTD in Runners, but not in Control animals, suggesting an increased involvement of NR2A subunits in LTD in animals that exercise. NVP‐AAM077 did not block LTD in NR2A Knock Out (KO) animals that exercised, as expected. In an attempt to discern whether NMDA receptors located at extrasynaptic sites could play a role in the induction of LTD, DL‐TBOA was used to block excitatory amino acid transport and increase extracellular glutamate levels. Under these conditions, LTD was not blocked by the co‐application of a specific NR2B subunit antagonist in either group, but NVP‐AAM077 again blocked LTD selectively in Runners. These results indicate that NR2A and NR2B subunits play a significant role in LTP in the DG, and that exercise can significantly alter the contribution of NMDA NR2A subunits to LTD. © 2007 Wiley‐Liss, Inc.
Functional dissociation between fornix and hippocampus in spatial conditional learning
Authors: Dumont J. , Petrides M. , Sziklas V.
Published: September 2007

Do lesions of the fornix or the hippocampus impair the performance of spatial conditional associative learning tasks, and to what extent does damage to these brain structures result in comparable deficits in this type of spatial behavior? The available evidence is not clear. In the present study, rats with lesions of the fornix, hippocampus, and normal control animals were trained on two spatial–visual conditional learning tasks in which they had to form arbitrary associations between visual stimuli and the context in which these stimuli were embedded. In one condition, rats were required to choose stimulus X in place A and stimulus Y in place B, and there was no overlap in the contents of the two scenes. In the other condition, the animal approached the same scene from two different directions and had to select stimulus X when the scene was viewed from perspective A and to select stimulus Y when the scene was viewed from perspective B. Rats with fornix transection were able to learn both conditional tasks at a rate comparable to that of normal control animals, but rats with hippocampal damage were severely impaired under both conditions. The findings extend the range of tasks known to be sensitive to damage of the hippocampus. In addition, the results argue that the fornix is not necessary for the acquisition of certain spatial conditional learning tasks and that this brain structure cannot be used as an indicator of hippocampal dysfunction under all learning situations. © 2007 Wiley‐Liss, Inc.
Biocompatibility testing of simulated total joint arthoplasty articulation debris
Authors: Anabtawi Mona , Beck Preston , Lemons Jack
Published: September 2007

Surface characterization was performed to evaluate the surface condition of an uncoated cobalt alloy disc (control), and discs with medium and thick boron coatings for total joint articulating surfaces. Discs were characterized by scanning electron microscopy before and after dissolution studies. Chemical analyses of elemental transfer to the solution were assessed to evaluate the surface stability of the new coating. An in vivo biocompatibility study for particulates [of boron (B), titanium alloy (Ti), cobalt alloy (Co), and combinations of B + Ti and B + Co] was performed using a rat air pouch model. The inflammatory reactions to particulates were evaluated histologically and histochemically. No physical alteration was seen in the discs after the dissolution studies, and the elemental transfer to the dissolution solution was minimal. The cytokines, tumor necrosis factor (TNFα), and histology results from these simulated debris showed similar and moderate level responses magnitudes for the boron and mixtures and the primary alloy particulates. The conclusion from this initial study was that assessments of the coated discs showed physical properties similar to control. Also results from the in vivo studies of simulated wear debris from boron coatings on titanium and cobalt alloys demonstrated biocompatibility profiles that were mild to moderate and similar to prior analyses of wear debris products in synovial pouch models. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008
Endothelial cell growth on silicon modified hydrogenated amorphous carbon thin films
Authors: Ogwu A. A. , Okpalugo T. I. T. , Ali N. , Maguire P. D. , McLaughlin J. A. D.
Published: September 2007

The biological response of human microvascular endothelial cells (HMEC‐1) seeded on Si‐DLC films and on control surfaces was evaluated in terms of initial cell enhancement, growth, and cytotoxicity. The microstructure of the films was characterised by Raman spectroscopy and X‐ray photoelectron spectroscopy. The effect of changes in microstructure, surface energy, surface electronic state, and electronic conduction, on the biological response of the films to endothelial cells was investigated. Endothelial cell adhesion and growth was found to be affected by changes in the microstructure of the films induced by silicon doping and thermal annealing. We observed a significant statistical difference in endothelial cell count between the as‐deposited DLC and Si‐DLC films using the one sample t‐test at a p‐value of 0.05. We also found a statistically significant difference between the adhesion of HMEC films on DLC and Si‐DLC films at various annealing temperatures using the one‐way ANOVA F statistic test at p < 0.05 and the post‐hoc Tukey test. One sample t‐test at p < 0.05 of MTT‐assay results showed the endothelial cells to be viable when seeded on DLC/Si‐DLC films. We suspect that the increased adhesion of endothelial cells induced by increasing the amount of silicon in the Si‐DLC films is associated with the development of a suitable surface energy due to silicon addition, which neither favored cell denaturing nor preferential water spreading before cellular attachment on the film surface. The presence of an external positively charged dipole on the Si‐DLC films confirmed by our Kelvin probe measurements is also expected to enhance the adhesion of endothelial cells that are well known to carry a negative charge. The Si‐DLC films investigated hold potential promise as coatings for haemocompatible artificial implants. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008
Plasmapheresis for hemolytic crisis and impending acute liver failure in Wilson disease
Authors: Asfaha Samuel , Almansori Mohammed , Qarni Uwais , Gutfreund Klaus S.
Published: September 2007

Wilsonian crisis is fatal unless copper removal is initiated early and liver transplantation is performed for patients that fulfill criteria for a poor outcome. We report a patient presenting with severe hemolysis and impending acute liver failure that made a rapid recovery with prompt initiation of plasmapheresis and chelation therapy. Rapid copper removal by plasmapheresis alleviated hemolysis and liver injury. A review of the literature was performed examining the use of plasmapheresis and albumin dialysis with continuous veno‐venous hemodialysis or molecular adsorbents and recirculating system. J. Clin. Apheresis, 2007. © 2007 Wiley‐Liss, Inc.
Calcium oxalate crystals in fetal bovine serum: Implications for cell culture, phagocytosis and biomineralization studies in vitro
Authors: Pedraza Claudio E. , Chien Yung‐Ching , McKee Marc D.
Published: September 2007

Cell culture methods and models are key investigative tools for cell and molecular biology studies. Fetal bovine serum (FBS) is commonly used as an additive during cell culture since its constituents promote cell survival, proliferation and differentiation. Here we report that commercially available FBS from different major suppliers consistently contain precipitated, calcium oxalate crystals—either in the monohydrate (COM) or dihydrate (COD) form. Mineral structure and phase identification of the crystals were determined by X‐ray diffraction, chemical composition by energy‐dispersive X‐ray microanalysis, and imaging and measurement of crystal growth steps by atomic force microscopy—all identified and confirmed crystallographic parameters for COM and COD. Proteins binding to the crystals were identified by immunoblotting, revealing the presence of osteopontin and fetuin‐A (α2HS‐glycoprotein)—known regulators of crystal growth found in serum. Macrophage cell cultures exposed to calcium oxalate crystals showed internalization of the crystals by phagocytosis in a process that induced disruption of cell–cell adhesion, release of reactive oxygen species and membrane damage, events that may be linked to the release of inflammatory cytokines by these cells into the culture media. In conclusion, calcium oxalate crystals found in commercially available FBS are toxic to cells, and their presence may confound results from in vitro studies where, amongst others, phagocytosis, biomineralization, renal cell and molecular biology, and drug and biomaterial testing are being examined. J. Cell. Biochem. 103: 1379–1393, 2008. © 2007 Wiley‐Liss, Inc.
Histone H1.2 is translocated to mitochondria and associates with bak in bleomycin‐induced apoptotic cells
Authors: Okamura Hirohiko , Yoshida Kaya , Amorim Bruna Rabelo , Haneji Tatsuji
Published: September 2007

Bleomycin induces single‐ and double‐stranded breaks in DNA, with consequent mitochondrial membrane aberrations that lead to the apoptotic cell death. It is poorly understood how DNA damage‐inducing apoptotic signals are transmitted to mitochondria, from which apoptotic factors are released into the cytoplasm. Here, we investigated the localization of histone H1.2 in the bleomycin‐treated human squamous carcinoma SCCTF cells. The presence of DNA double‐strand breaks in the bleomycin‐treated cells was examined by Western analysis using antibody against phosphorylated histone H2AX (γ‐H2AX). Incubation of SCCTF cells for 48 h with 10 µM bleomycin induced apoptosis, as determined by cleavage of lamin B1 to 28 kDa fragment and DNA ladder formation. The mitochondrial permeabilization causing apoptotic feature was also detected with MitoCapture in the bleomycin‐treated cells. Histone H1.2 was translocated from the nucleus to the mitochondria after treatment with bleomycin and co‐localized with Bak in mitochondria. Our present results suggest that histone H1.2 plays an important role in transmitting apoptotic signals from the nucleus to the mitochondria following double‐stranded breaks of DNA by bleomycin. J. Cell. Biochem. 103: 1488–1496, 2008. © 2007 Wiley‐Liss, Inc.
Catalase overexpression impairs TNF‐α induced NF‐κB activation and sensitizes MCF‐7 cells against TNF‐α
Authors: Lüpertz Regine , Chovolou Yvonni , Kampkötter Andreas , Wätjen Wim , Kahl Regine
Published: September 2007

The pleiotropic cytokine tumor necrosis factor alpha (TNF‐α) can induce apoptosis but also supports cell survival pathways. Among the possible anti‐apoptotic mechanisms of TNF‐α is the activation of the transcription factor NF‐κB. Since reactive oxygen species (ROS) are assumed to contribute to TNF‐α mediated cytotoxicity but can also facilitate NF‐κB activation this study investigates the relationship between TNF‐α treatment, NF‐κB activation and the expression of the anti‐oxidative enzyme catalase. TNF‐α treatment caused downregulation of catalase expression in MCF‐7, Caco‐2 and Hct‐116 cancer cell lines. Overexpression of catalase in MCF‐7 cells, resulting in lower intracellular ROS levels upon challenge with H2O2, caused a transient nuclear p65 translocation upon TNF‐α treatment as compared to the sustained NF‐κB activation in wild type cells. This was due to a lack of sufficient H2O2 to co‐stimulate NF‐κB activation as demonstrated by the observation that addition of exogenous H2O2 led to a second increase of NF‐κB activity. The rapid decline of nuclear translocation of NF‐κB in the catalase overexpressing cells resulted in a slower increase of NF‐κB mediated reporter gene expression. These results indicate that TNF‐α mediated downregulation of catalase expression and accordingly sufficient H2O2 is required for appropriate function of the NF‐κB dependent survival pathway. J. Cell. Biochem. 103: 1497–1511, 2008. © 2007 Wiley‐Liss, Inc.
The vitamin D receptor‐mediated activation of phosphatidylinositol 3‐kinase (PI3Kα) plays a role in the 1α,25‐dihydroxyvitamin D3‐stimulated increase in steroid sulphatase activity in myeloid leukaemic cell lines
Authors: Hughes Philip J. , Lee Jimmy S. , Reiner Neil E. , Brown Geoffrey
Published: September 2007

In this article we show that 1α,25‐dihydroxyvitamin D3 (1α,25(OH)2D3) stimulates the activity of the class IA phosphatidylinositol 3‐kinase PI3Kα and its downstream target Akt in HL60, U937 and THP‐1 myeloid leukaemic cell lines. Furthermore, we show that the classical nuclear vitamin D receptor (VDRnuc) is involved in this activation of the PI3K/Akt signalling in these cell lines. We have previously shown that the activity of steroid sulphatase is stimulated in HL60, U937 and THP‐1 myeloid leukaemic cell lines by 1α,25(OH)2D3 (Hughes et al., [2001] Biochem J 355:361–371; Hughes et al., [2005] J Cell Biochem 94:1175–1189; Hughes and Brown [2006] J Cell Biochem 98:590–617). In this article we show that the 1α,25(OH)2D3‐stimulated increase in signalling via the PI3K/Akt pathway plays a role in the increase in steroid sulphatase activity in the HL60 U937 and THP‐1 cell lines. We used a variety of pharmacological and biochemical approaches to show that activation of PI3Kα mediates the 1α,25(OH)2D3‐stimulated increase in steroid sulphatase activity in myeloid leukaemic cells. We also show that the PI3K/Akt dependent activation of NF‐κB plays a role in the 1α,25(OH)2D3‐stimulated increase in steroid sulphatase activity in myeloid leukaemic cells. J. Cell. Biochem. 103: 1551–1572, 2008. © 2007 Wiley‐Liss, Inc.
Mouse spermatozoa contain a nuclease that is activated by pretreatment with EGTA and subsequent calcium incubation
Authors: Boaz Segal M. , Dominguez Kenneth , Shaman Jeffrey A. , Ward W. Steven
Published: September 2007

We demonstrated that mouse spermatozoa cleave their DNA into ∼50 kb loop‐sized fragments with topoisomerase IIB when treated with MnCl2 and CaCl2 in a process we term sperm chromatin fragmentation (SCF). SCF can be reversed by EDTA. A nuclease then further degrades the DNA in a process we term sperm DNA degradation (SDD). MnCl2 alone could elicit this activity, but CaCl2 had no effect. Here, we demonstrate the existence of a nuclease in the vas deferens that can be activated by ethylene glycol tetraacetic acid (EGTA) to digest the sperm DNA by SDD. Spermatozoa were extracted with salt and dithiothreitol to remove protamines and then incubated with EGTA. Next, the EGTA was removed and divalent cations were added. We found that Mn2+, Ca2+, or Zn2+ could each activate SDD in spermatozoa but Mg2+ could not. When the reaction was slowed by incubation on ice, EGTA pretreatment followed by incubation in Ca2+ elicited the reversible fragmentation of sperm DNA evident in SCF. When the reactions were then incubated at 37°C they progressed to the more complete degradation of DNA by SDD. EDTA could also be used to activate the nuclease, but required a higher concentration than EGTA. This EGTA‐activatable nuclease activity was found in each fraction of the vas deferens plasma: in the spermatozoa, in the surrounding fluid, and in the insoluble components in the fluid. These results suggest that this sperm nuclease is regulated by a mechanism that is sensitive to EGTA, possibly by removing inhibition of a calcium binding protein. J. Cell. Biochem. 103: 1636–1645, 2008. © 2007 Wiley‐Liss, Inc.
Serine protease inhibitors N‐α‐Tosyl‐L‐Lysinyl‐Chloromethylketone (TLCK) and N‐Tosyl‐L‐Phenylalaninyl‐Chloromethylketone (TPCK) are potent inhibitors of activated caspase proteases
Authors: Frydrych Ivo , Mlejnek Petr
Published: September 2007

Serine protease inhibitors N‐α‐tosyl‐L‐lysinyl‐chloromethylketone (TLCK) and N‐tosyl‐L‐phenylalaninyl‐chloromethylketone (TPCK) exhibit multiple effects on cell death pathways in mammalian cells. Thus, they are able to induce apoptosis by itself or promote cell death induced by other cytotoxic stimuli [King et al., 2004; Murn et al., 2004]. On the other hand, TLCK and TPCK were reported to prevent apoptosis by inhibiting the processing of caspases in response to some cell death inducing stimuli [Stefanis et al., 1997; Jones et al., 1998]. We observed that the pretreatment of HL‐60 cells with TLCK or TPCK diminished caspases 3 and ‐7 (DEVDase) and caspase‐6 (VEIDase) activity in response to various cell death inducing stimuli such as staurosporine (STS), etoposide (ETP), or N6‐(2‐isopentenyl)adenosine. In addition, TLCK but not TPCK inhibited collapse of mitochondrial transmembrane potential ΔΨm (delta psi) in dying HL‐60 cells. Such effects used to be considered as protective, however, the protection was only presumable since neither TLCK nor TPCK actually prevented cells from death. Our results further indicated that serine protease inhibitors TLCK and particularly TPCK acted as efficient direct inhibitors of mature caspases. Indeed, experiments with human recombinant caspases provided unequivocal evidence that TLCK and TPCK are very potent but non‐specific inhibitors of activated caspases, namely caspases 3, ‐6, and ‐7. Interestingly, TPCK exhibited similar efficiency towards human recombinant caspases to that found for panspecific caspase inhibitor Boc‐D‐CMK. Such properties of TLCK and TPCK, previously considered as specific inhibitors of serine proteases, might offer novel consistent explanation for several protective or protective‐like effects on apoptotic cells. J. Cell. Biochem. 103: 1646–1656, 2008. © 2007 Wiley‐Liss, Inc.
p63 in prostate biology and pathology
Authors: Grisanzio Chiara , Signoretti Sabina
Published: September 2007

The identification of stem cells and differentiation programs regulating the development and maintenance of the normal prostate epithelium is essential for the identification of the cell type(s) and molecular alterations involved in the development and propagation of prostate cancer (CaP). The p53‐homologue p63 is highly expressed in normal prostate basal cells and is a clinically useful biomarker for the diagnosis of CaP. Importantly, p63 has been shown to play a critical role in prostate development. Recent experimental evidence also suggests that this gene is essential for normal stem cell function in the prostate as well as other epithelial organs. Future studies aimed at better defining the role of p63 in the renewal of the adult prostate epithelium are likely to shed new light on the mechanisms involved in prostate carcinogenesis. J. Cell. Biochem. 103: 1354–1368, 2008. © 2007 Wiley‐Liss, Inc.
The use of solvent isotope effects in the pursuit of enzyme mechanisms
Authors: Schowen Richard L.
Published: September 2007

The basic principles and illustrative applications to enzyme mechanisms of solvent isotope effects, with emphasis on the use of rate measurements in mixtures of protium and deuterium oxides (‘proton inventories’), are reviewed over a period slightly shorter than the history of this Journal. The principles in their current formulation are traced to publications of the 1960s and the illustrations are taken from publications that have appeared in 2006–2007. Copyright © 2007 John Wiley & Sons, Ltd.
Isotope effects for fluorine‐18 and carbon‐11 in the study of reaction mechanisms
Authors: Matsson Olle , MacMillar Susanna
Published: September 2007

The use of kinetic isotope effects (KIEs) for the short‐lived radionuclides 11C and 18F in the study of reaction mechanisms is described using some examples. Leaving group fluorine KIEs (k18/k19) have been utilized to determine the rate‐limiting step for nucleophilic aromatic substitution reactions (SNAr). The fluorine KIE was also used to probe the effect of changing solvent and nucleophile steric hindrance on rate‐limiting step. The mechanism for a base promoted elimination reaction was determined to be stepwise (E1cB) by a multiple KIE study including the leaving group fluorine KIE. The transition state structures for aliphatic nucleophilic substitution reactions (SN2) have been investigated by multiple KIE studies for cases where the substrate substitution, leaving group or solvent has been varied. Carbon KIEs for labelled α‐carbon atom in the substrate are large, k11/k14 = 1.189–1.220. For labelled nucleophile cyanide ion, k11/k14 = 0.99951–1.0119. Copyright © 2007 John Wiley & Sons, Ltd.
The synthesis of tritiated (R)‐2‐methoxy‐N‐n‐propyl‐nor‐apomorphine (MNPA)
Authors: Malmquist Jonas , Olofsson Susanne , Ström Peter
Published: September 2007

A method for the preparation of [3H]‐MNPA ((R)‐2‐methoxy‐N‐n‐propyl‐norapomorphine) has been developed addressing the regioisomer problem as well as the oxidation problem. (R)‐2, 10, 11‐trihydroxy‐N‐n‐propyl‐norapomorphine was protected with 10, 11‐dibenzyl or 10, 11‐acetonide. The pure precursor was then methylated using [3H]‐methyliodide. The product was isolated after deprotection and high‐pressure liquid chromatography (HPLC) purification. Ascorbic acid was used as an antioxidant in the HPLC eluent and the stock solution. Characterization of the intermediates and products with 3H‐ and 1H‐NMR was performed. A specific activity of 3.1 TBq/mmol (83.8 Ci/mmol) and 98.9% purity was obtained. Copyright © 2007 John Wiley & Sons, Ltd.