bluuebunny/crossref_metadata_2025 huggingface dataset:
Römische Kalkbrennerei in Iversheim/Eifel
Authors: Schwedt Georg
Published: April 2008

In einer ausgegrabenen römischen Kalkbrennerei am Rande der Eifel – in Iversheim bei Bad Münstereifel, direkt an der Bahnlinie und B 51 – kann sich der Besucher über die Technik vor fast 2000 Jahren informieren. Die Kalkbrennerei wurde beim Verlegen einer Wasserleitung entdeckt und 1966 bis 1968 ausgegraben.
Von Mücken lernen
Authors: Harrer Roswitha
Published: April 2008

Besucher von zoologischen Gärten kennen die kleine Windmaschine am Eingang der Tropenhäuser, die die beschlagene Brille wieder von den kondensierten Wassertröpfchen befreien soll. Gegen das lästige Beschlagen könnte möglicherweise auch eine besondere Oberflächenbeschichtung helfen, die das Anheften der winzigen Wassertröpfchen gar nicht erst zulässt.
DNA‐Kräne und ‐Baumaterial
Authors: Groß Michael
Published: April 2008

Die Natur benutzt die wohldefinierte Doppelhelixstruktur zur effizienten und erstaunlich fehlersicheren Informationsverarbeitung. Im Labor kann man dieses Prinzip allerdings auch auf den Kopf stellen und die Sequenzinformation der DNA so manipulieren, dass gewünschte Struktur‐elemente und sogar mechanisch steuerbare Maschinenteile entstehen.
RNA‐Chaperone mit Breitbandwirkung
Authors: Hille‐Rehfeld Annette
Published: April 2008

RNA‐Chaperone sind beim Entfalten der räumlichen Strukturen von Ribonucleinsäuren nicht wählerisch und können selbst die stabile native Konformation auflösen. Wie durch ihre Aktivität dennoch die funktionell bedeutsame native RNA‐Struktur begünstigt wird, zeigt die Untersuchung eines Ribozyms aus dem Schlauchpilz Neurospora crassa.
A variable field strength system for hyperpolarized noble gas MR imaging of rodent lungs
Authors: Dominguez‐Viqueira William , Parra‐Robles Juan , Fox Matthew , Handler William B. , Chronik Blaine A. , Santyr Giles E.
Published: April 2008

Hyperpolarized Noble Gas (HNG), 3He (helium) or 129Xe (xenon), MR imaging has become a promising approach for visualizing lung anatomy and function. It has been theoretically predicted that low field strengths (0.05–0.2 T) may provide optimal signal‐to‐noise ratio (SNR) and spatial resolution for clinical HNG MR imaging. These optimum field strengths correspond to frequencies between 1.62–6.5 MHz and 0.59–2.35 MHz for 3He and 129Xe respectively. The optimum field strength depends on the size and geometry of the sample and radiofrequency (RF) coil as well as the field dependence of the HNG MR properties in the lung (e.g., relaxation times, susceptibility effects). In particular, little is known about the field dependence of the apparent transverse relaxation time, T, which is expected to strongly influence HNG signal. In this paper, a broadband (0.1–100 MHz) variable field strength MR imaging system for rodents is described. A custom‐built resistive magnet was constructed and shimmed to provide the necessary homogeneity for imaging. RF coils and transmit/receive switches for different frequencies were also developed. Preliminary proton (1H) and hyperpolarized 129Xe images of test objects are presented, including a desiccated lung phantom. In vivo 129Xe signals from rat lungs were acquired at 73.5 mT and T was estimated to be approximately 80 ± 8 ms, in good agreement with previously reported values. The MR system developed should be useful for imaging rodent lungs at different field strengths to verify the expected SNR and spatial resolution possible using HNG imaging and to investigate long range diffusion and oxygen‐induced transverse relaxation. © 2008 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 33B: 124–137, 2008
B1 inhomogeneity effect reduction for 2D spatial selective RF pulse using simulated annealing
Authors: Pang Yong , Shen Gary X.
Published: April 2008

With the development of the high‐field MRI system, the RF field inhomogeneity becomes a challenging problem in high flip angle excitation. In this study, a new RF pulse design method is proposed, which combines the simulated annealing (SA) algorithm and the k‐space method to attain a pulse which can compensate the RF field inhomogeneity effect. The RF pulse envelope is firstly initiated using the k‐space method and a cost function which contains the passband error and stopband error is defined. Then the SA is applied to refine the RF pulse shape to achieve low‐cost value. Finally, under inhomogeneous RF field an optimized RF pulse with improved flip angle accuracy can be obtained. Simulation results show that when compared with the pulse designed only using the k‐space method, the passband error can be decreased by 28%, 40%, and 75% for 90° excitation pulse, refocusing pulse, and 180° inversion pulse, respectively. © 2008 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 33B: 75–83, 2008
Mechanism‐Guided Improvements to the Single Molecule Oxidation of Carbon Nanotube Sidewalls
Authors: Coroneus John G. , Goldsmith Brett R. , Lamboy Jorge A. , Kane Alexander A. , Collins Philip G. , Weiss Gregory A.
Published: April 2008

Real‐time monitoring of carbon nanotube conductance during electrochemical and chemical etching reveals the electronic signatures of individual bond alteration events on the nanotube sidewall. Tracking the conductance of multiple single‐molecule experiments through different synthetic protocols supports putative mechanisms for sidewall derivatization. Insights gained from these mechanistic observations imply the formation of sidewall carboxylates, which are useful as handles for bioconjugation. We describe an electronic state required for efficacious chemical treatment. Such real‐time monitoring can improve carboxylate yields to 45 % or more. The experiments illustrate the power of molecular nanocircuits to uncover and direct the mechanisms of chemical reactions.
Dynamics of the Size Distribution of CdTe Quantum Dot Ensembles during Growth in Liquid and Crystalline Phases
Authors: Piepenbrock Marc‐Oliver M. , Stirner Tom , O'Neill Mary , Kelly Stephen M.
Published: April 2008

We recently reported that the growth rate of colloidal CdTe nanoparticles decreases by orders of magnitude when the particles undergo a phase transition from liquid to crystal. The dynamics of nanoparticle growth are dominated by this factor rather than the size dependence of the chemical potential. Herein we discuss how the phase transition affects the size distribution and photoluminescence quantum efficiency of the nanoparticles. We suggest that the absorption linewidth is a better monitor of size distribution than the photoluminescence linewidth because the photoluminescence quantum efficiency, which affects the latter via energy transfer, varies substantially with reaction time. We find that the size distribution broadens in the early stages of growth possibly because of inhomogeneities in the phase transition radius or because particles nucleated at later times coalesce with nanocrystals. The quantum efficiency is enhanced when tellurium is depleted in the reaction solution, giving a cadmium‐enriched surface. Batches with high initial tellurium and cadmium concentrations show a substantial amount of delayed nucleation, lower quantum efficiency and some anisotropic growth.
Skills needed to help communities manage natural resource conflicts
Authors: Singletary Loretta , Smutko L. Steven , Hill George C. , Smith Marilyn , Daniels Steven E. , Ayres Janet S. , Haaland Kay
Published: April 2008

Competition for natural resources has spawned unprecedented conflict between users, resulting in litigious and legislative actions. Citizens often expect Cooperative Extension professionals to engage communities in collaborative processes to manage these conflicts. This paper examines thirty‐five skills Cooperative Extension professionals need if they are to engage communities in collaborative processes. Survey methodology is used to assess the skills extension professionals perceive as most needed, and the ranked means of the perceived skill needs are presented. The results offer information useful to strengthen the capacity of extension professionals to play an important role in helping citizens manage natural resource conflicts.
Communication strategies in early adolescent conflict: An attributional approach
Authors: Scott Whitney
Published: April 2008

This study used attribution theory to investigate how attributions of responsibility influence early adolescents' communication strategy preference during friendship conflicts. It was hypothesized that selfresponsibility would be related to more cooperative ways of communicating (integrative strategies), whereas perceptions of other‐responsibility would be related to less cooperative ways of communicating (distributive or passive strategies). Participants ( N = 67) between the ages of twelve and fourteen read hypothetical conflict scenarios and described how they would communicate to resolve the conflict. Partial support for the hypothesis was found; however, complex details, such as the conflict theme and use of multicommunication strategies, were important variables in the resolution process. Conflict resolution programs, mediators, and clinicians might consider these complex aspects in trainings and practice.
CD137 ligand reverse signaling has multiple functions in human dendritic cells during an adaptive immune response
Authors: Lippert Undine , Zachmann Karolin , Ferrari David M. , Schwarz Herbert , Brunner Edgar , Latif A. H. M. Mahbub‐ul , Neumann Christine , Soruri Afsaneh
Published: April 2008

T cell activation via dendritic cells (DC) is an important step in the adaptive immune response, which requires DC maturation, migration to lymph nodes and presentation of antigen to T cells. CD137 receptor expressed on activated T cells is a potent costimulatory molecule. Here, we investigated the functions of CD137 ligand (CD137L) in human monocyte‐derived DC during an immune response. Cross‐linking of CD137L on DC leads to cell maturation in an autocrine fashion, mostly via release of TNF‐α. Reverse signaling of CD137L also mediates migration of DC via up‐regulation of the CCR7 chemokine receptor, demonstrated by an in vivo MIP‐3β‐dependent SCID mouse migration model. Finally, CD137L‐activated DC induce differentiation of human T cells into potent Th1 effectors. Cocultivation of autologous T cells and CD137L‐activated DC in an antigen‐specific reaction leads to T cell proliferation and the release of IL‐12p70 and IFN‐γ. These findings deliver new insights into the multiple effects of reverse signaling of CD137L in human DC during the initiation of an adaptive immune response, including the key features of DC maturation, migration and, ultimately, antigen‐specific T cell differentiation.
Clinical application of regulatory T cells for treatment of type 1 diabetes and transplantation
Authors: Brusko Todd , Bluestone Jeffrey
Published: April 2008

Immune regulation is a complex process that depends on the maintenance of self tolerance while retaining robust immune responses against microbes. The emergence of Treg as a central mechanism for immune regulation has generated a new paradigm where Treg‐resistant memory T cells and/or “defective” Treg lead to a breakdown in tolerance resulting in immune pathology. In this perspective, we highlight the opportunities and challenges in the field of Treg therapy.

See accompanying commentary: http://dx.doi.org/10.1002/eji.200738107
Critical role of IL‐2 and TGF‐β in generation, function and stabilization of Foxp3+CD4+ Treg
Authors: Horwitz David A. , Zheng Song Guo , Wang Juhua , Gray J. Dixon
Published: April 2008

CD4+Foxp3+ Treg consist of two indistinguishable subsets induced in either the thymus or the periphery. In addition to their suppressive activities, IL‐6 can convert natural Treg to pro‐inflammatory IL‐17‐producing cells, but those induced with IL‐2 and TGF‐β remain Treg. Unlike mouse CD4+CD25– cells, which rapidly become polyclonal Foxp3+CD25+ Treg when activated appropriately with IL‐2 and TGF‐β, human T cells require multiple stimulations to become similar suppressor cells.

See accompanying commentary: http://dx.doi.org/10.1002/eji.200738111
How many mechanisms do regulatory T cells need?
Authors: Vignali Dario
Published: April 2008

A plethora of new regulatory T cell (Treg) mechanisms have recently emerged. This raises two important questions. First, how many molecules or mechanisms are required for Treg to work? Second, how should we evaluate the contribution of any given Treg molecule/mechanism and how is this likely to relate (or not) to the phenotype seen in Scurfy/Foxp3‐deficient mice? In this discussion piece, I will briefly outline our current understanding of the Treg arsenal and address these important questions.

See accompanying commentary: http://dx.doi.org/10.1002/eji.200838143
Role of Foxp3‐positive regulatory T cells during infection
Authors: Belkaid Yasmine
Published: April 2008

Surviving an infection requires the generation of an immune response that controls the invading pathogen while limiting collateral damage to self tissues that may result from an exuberant immune response. Various populations of regulatory cells, including Foxp3+ Treg, have been shown to play a central role in the establishment of these controlled immune responses. In this review, I discuss current hypotheses and points of polemic associated with the origin, mode of action and antigen specificity of Foxp3+ Treg during infection.

See accompanying commentary: http://dx.doi.org/10.1002/eji.200738104
Regulatory T cells and immune computation
Authors: Quintana Francisco J. , Cohen Irun R.
Published: April 2008

The role of Treg in immune regulation is the topic of this Viewpoint series in the European Journal of Immunology (EJI); the question to be discussed in this section is the effector function of Treg in immune regulation. In this manuscript, we take on the following three postulates outlined by Rolf Zinkernagel on the role of Treg in the control of immunity. First, the immune response is regulated primarily by the antigen and not by Treg. Second, immune non‐responsiveness results from the deletion of specific receptor‐bearing T cells. Third, there is no definitive proof of the existence of specialized Treg that know what is needed for an equilibrated immune response. Herein, we discuss data demonstrating the existence of specialized Treg and therefore arguing against the validity of the first two postulates. However, based on the reactive nature of the immune system, we agree with Rolf’s third postulate in that Treg cannot know ahead of time an ideal set‐point for immune homeostasis.

See accompanying commentary: http://dx.doi.org/10.1002/eji.200738114
The Noncarbonylative Photochemistry of Group 6 Fischer Carbene Complexes
Authors: Fernández Israel , Sierra Miguel A. , Mancheño María José , Gómez‐Gallego Mar , Cossío Fernando P.
Published: April 2008

The different photochemical reaction mechanisms of group 6 Fischer carbene complexes have been studied by a joint experimental and density functional theory (DFT) computational study. This study unifies the photochemcal behavior of group 6 metal carbene complexes (M = Cr or W), which may occur by three different photoreactions, namely photocarbonylation, stepwise 1,2‐dyotropic rearrangement, and α‐fragmentation. The metal atom and the substituent on the nitrogen atom attached to the carbene carbon atom influence the topography of the potential energy surface, which leads to two different activated species, diradicals or metallacyclopropanones. Complexes having a hydrogen substituent at the nitrogen atom experience a stepwise dyotropic migration with no significant differences between the chromium‐ and tungsten–carbene complexes. The excitation of complexes having substituents other than hydrogen at the nitrogen atom leads to two different T1 species, and hence to the formation of mixtures of products arising from α‐fragmentation (noncarbonylation) and amino esters (photocarbonylation). The two triplet states are isoenergetic in the Cr derivatives, but the T1 species that leads to α‐fragmentation is strongly favored for the W derivatives. Finally, both the chromium‐ and tungsten–carbene complexes are photoreactive in spite of the longstanding claim that tungsten–carbene complexes were photochemically inert. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Helical Porphyrinoids: Incorporation of Ferrocene Subunits into Macrocyclic Structures
Authors: Stępień Marcin , Simkowa Irena , Latos‐Grażyński Lechosław
Published: April 2008

Ferrocene‐containing porphyrinoids have been synthesized in which ferrocene‐1,1′‐diyl units are linked to a dipyrrin or thiatripyrrin to form macrocyclic structures. NMR spectroscopic evidence shows that these new systems adopt helical conformations that undergo an inversion process in solution. In addition, small amounts of unexpected scrambling products have been isolated and characterized, namely a dipyrrin‐bisferrocenophane and two expanded bis(ferrocene) macrocycles. The formation of these systems, which contain macrocyclic rings of different sizes, is a consequence of the structural flexibility of the ferrocene unit. Cyclic voltammetry shows that ferrocene oxidation is reversible in all the systems reported here, and that it is finely tuned by the properties of the ring system. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Direct Electrochemistry of Hemoglobin Entrapped in Composite Electrodeposited Chitosan‐Multiwall Carbon Nanotubes and Nanogold Particles Membrane and Its Electrocatalytic Application
Authors: Liu Chuanyin , Hu Jiming
Published: April 2008

Hemoglobin was entrapped in composite electrodeposited chitosan‐multiwall carbon nanotubes (MCNTs) film by assembling gold nanoparticles and hemoglobin step by step. In phosphate buffer solution (pH 7), a pair of well‐defined and quasireversible redox peaks appeared with formal potential at −0.289 V and peak separation of 100 mV. The redox peaks respected for the direct electrochemistry of hemoglobin at the surface of chitosan‐MCNTs‐gold nanoparticles modified electrode. The parameters of experiments have also been optimized. The composite electrode showed excellent electrocatalysis to peroxide hydrogen and oxygen, the peak current was linearly proportional to H2O2 concentration in the range from 1×10−6 mol/L to 4.7×10−4 mol/L with a detection limit of 5.0×10−7 mol/L, and this biosensor exhibited high stability, good reproducibility and better selectivity. The biosensor showed a Michaelis–Menten kinetic response as H2O2 concentration is larger than 5.0×10−4 mol/L, the apparent Michaelis–Menten constant for hydrogen peroxide was calculated to be 1.61 μmol/L.
Ordered Mesoporous Carbon Paste Electrodes for Electrochemical Sensing and Biosensing
Authors: Zhu Liande , Tian Chunyuan , Zhu Dongxia , Yang Ruilan
Published: April 2008

Surface renewable ordered mesoporous carbon paste electrodes (OMCPE) were prepared by mechanical mixing ordered mesoporous carbon (OMC) and mineral oil. Electrochemical behavior of the composite electrode was evaluated and compared with the conventional graphite paste (GPE) and carbon nanotubes paste (CNTPE) electrodes. The OMCPE provided improved electron transfer kinetics and catalytic capabilities in connection with oxidation and/or reduction of different redox systems, such as ferricyanide and some biological species, e. g. ascorbic acid (AA), uric acid (UA), β‐nicotinamide adenine dinucleotide (NADH), dopamine (DA), epinephrine (EP), acetaminophenol (AP) and hydrogen peroxide. The substantial decrease in the over voltage of the hydrogen peroxide oxidation along with the facile incorporation of glucose oxidase (GOD) into the composite matrix allowed us successfully to fabricate a sensitive and selective glucose biosensor. A linear response up to 15 mM glucose was obtained for the OMCPE modified with 10% GOD (w/w) with a detection limit of 0.072 mM. In addition, we also successfully applied the OMCPE to the anodic stripping voltammetric analysis of heavy metal ions with improved sensitivities in comparison with CNTPE and GPE. The excellent experimental results implicate that the new developed paste electrode holds great promise in the design of electrochemical devices, such as sensors and biosensors.
Photo‐Induced Electron Transfer Between Photosystem 2 via Cross‐linked Redox Hydrogels
Authors: Badura Adrian , Guschin Dmitrii , Esper Berndt , Kothe Tim , Neugebauer Sebastian , Schuhmann Wolfgang , Rögner Matthias
Published: April 2008

Photosystem 2 (PS2) that catalyses light driven water splitting in photosynthesis was ‘wired’ to electrode surfaces via osmium‐containing redox polymers based on poly(vinyl)imidazol. The redox polymer hydrogel worked as both immobilization matrix and electron acceptor for the enzyme. Upon illumination, the enzymatic reaction could be switched on and a catalytic current was observed at the electrode. The catalytic current is directly dependent on the intensity of light used for the excitation of PS2. A typical current density of 45 μA cm−2at a light intensity of 2.65 mW cm−2could be demonstrated with a significantly improved operational stability.
Chromosome 11 genomic changes in parathyroid adenoma and hyperplasia: Array CGH, FISH, and tissue microarrays
Authors: Yi Y. , Nowak Norma J. , Pacchia Annmarie L. , Morrison Carl
Published: April 2008

We have used a combination of gene expression profiling, array comparative genomic hybridization (aCGH), fluorescent in situ hybridization (FISH) and tissue microarrays (TMAs) to investigate chromosome 11 genetic changes in subsets of benign parathyroid tumors. Integration of gene expression profiling and aCGH was done using differential gene locus mapping analysis. We have identified three distinct relatively common chromosome 11 genomic changes in various subsets of parathyroid tumors. The simplest and least common of these genomic changes involves translocation of the CCND1 gene with subsequent strong CCND1 expression. This genetic change is essentially limited to parathyroid adenomas (8%), although expression of CCND1 without translocation is common in uremic hyperparathyroidism. Not surprisingly, deletion of the MEN1 locus at 11q13 or loss of a large portion or an entire chromosome 11 was a common finding. This particular genomic change appears to have a prominent effect on the overall results of gene expression profiling and was present in slightly less than one‐half of adenomas. Genomic changes in primary nonfamilial hyperplasia were for the most part restricted to 11q13 deletion or loss of chromosome 11. The third genomic change we identified was 11q23 deletion. This genetic change was relatively independent of other chromosome 11 changes and present in slightly less than one‐half of adenomas. 11q23 deletion along with relatively strong CCND1 expression was common in uremic hyperparathyroidism. © 2008 Wiley‐Liss, Inc.
Microhomologies and interspersed repeat elements at genomic breakpoints in chronic myeloid leukemia
Authors: Mattarucchi Elia , Guerini Vittoria , Rambaldi Alessandro , Campiotti Leonardo , Venco Achille , Pasquali Francesco , Lo Curto Francesco , Porta Giovanni
Published: April 2008

Reciprocal translocation t(9;22) is central to the pathogenesis of chronic myeloid leukemia. Some authors have suggested that Alu repeats facilitate this process, but supporting analyses have been sparse and often anecdotal. The purpose of this study was to analyze the local structure of t(9;22) translocations and assess the relevance of interspersed repeat elements at breakpoints. Collected data have been further compared with the current models of DNA recombination, in particular the single‐strand annealing (SSA) and the nonhomologous end joining (NHEJ) processes. We developed a protocol for the rapid characterization of patient‐specific genomic junctions and analyzed 27 patients diagnosed with chronic myeloid leukemia. Sequence analysis revealed microhomologies at the junctions of 21 patients of 27, while interspersed repeats were of relevance (P < 0.05) in at least 16 patients. These findings are more frequent than expected and give an indication that the main mechanisms involved in the t(9;22) translocation are the SSA and NHEJ pathways, both playing a role. Furthermore, our report is consistent with microhomologies facilitating the joining of DNA ends in the translocation process, and with both Alu and a variety of other repeat sequences pairing nonhomologous chromosomes during the SSA pathway. © 2008 Wiley‐Liss, Inc.
Two case studies illustrating how relatively selective hippocampal lesions in humans can have quite different effects on memory
Authors: Holdstock J.S. , Parslow D.M. , Morris R.G. , Fleminger S. , Abrahams S. , Denby C. , Montaldi D. , Mayes A.R.
Published: April 2008

Two patients, with magnetic resonance imaging (MRI)‐confirmed relatively selective hippocampal damage, showed distinct patterns of performance on tests of recall, item recognition, and associative recognition. Patient AC showed a mean bilateral volume reduction of the hippocampus of 28%, but displayed no memory deficit. Both recall and recognition memory were unimpaired. In contrast, patient PR, who showed a mean bilateral hippocampal volume reduction of 59%, was more consistently impaired on recall than recognition tests, although his recognition scores were highly variable. Patients AC and PR illustrate how variable the memory deficit following seemingly selective hippocampal damage can be in humans. They highlight the need for more sophisticated imaging in future studies if the human hippocampus' role in memory is to be fully identified. © 2008 Wiley‐Liss, Inc.
Associations between mothers' sensitivity to their infants' internal states and children's later understanding of mind and emotion
Authors: Ereky‐Stevens Katharina
Published: April 2008

This study investigated associations between mother–infant interactions and children's subsequent understanding of mind and emotion. Mothers' tendency to comment on their infants' internal world and their general sensitivity to their infants' internal states were measured through coded play interactions at 10 months. The latter measurement included ratings on four aspects of maternal behaviour: mindful facilitation, joint attention commenting, pacing, and affect catching. In contrast to mothers' internal state language, these behaviours did not tap mothers' explicit linguistic representation of their infants' mental states. At 54 months, children's understanding of mind and emotion was measured through a range of false‐belief tasks and an emotion‐understanding task. Multivariate analysis revealed direct positive links between mothers' sensitivity to their infants' internal states and children's later understanding of mind. Copyright © 2008 John Wiley & Sons, Ltd.
Gene expression changes during HPV‐mediated carcinogenesis: A comparison between an in vitro cell model and cervical cancer
Authors: Wan Fang , Miao Xijiang , Quraishi Iram , Kennedy Valerie , Creek Kim E. , Pirisi Lucia
Published: April 2008

We used oligonucleotide microarrays to investigate gene expression changes associated with multi‐step human papillomavirus type 16 (HPV16)‐mediated carcinogenesis in vitro. Gene expression profiles in 4 early passage HPV16‐immortalized human keratinocyte (HKc) lines derived from different donors were compared with their corresponding 4 late‐passage, differentiation‐resistant cell lines, and to 4 pools of normal HKc, each composed of 3 individual HKc strains, on Agilent 22 k human oligonucleotide microarrays. The resulting data were analyzed using a modified T‐test coded in R to obtain lists of differentially expressed genes. Gene expression changes identified in this model system were then compared with gene expression changes described in published studies of cervical intraepithelial neoplasia (CIN) and cervical cancer. Common genes in these lists were further studied by cluster analysis. Genes whose expression changed in the same direction as in CIN or cervical cancer (concordant) at late stages of HPV16‐mediated transformation in vitro formed one major cluster, while those that changed in the opposite direction (discordant) formed a second major cluster. Further annotation found that many discordant expression changes involved gene products with an extracellular localization. Two novel genes were selected for further study: overexpression of SIX1 and GDF15, observed during in vitro progression in our model system, was confirmed in tissue arrays of cervical cancer. These microarray‐based studies show that our in vitro model system reflects many cellular and molecular alterations characteristic of cervical cancer, and identified SIX1 and GDF15 as 2 novel potential biomarkers of cervical cancer progression. © 2008 Wiley‐Liss, Inc.
Heregulin‐induced activation of ErbB3 by EGFR tyrosine kinase activity promotes tumor growth and metastasis in melanoma cells
Authors: Ueno Yoko , Sakurai Hiroaki , Tsunoda Satoshi , Choo Min‐Kyung , Matsuo Mitsuhiro , Koizumi Keiichi , Saiki Ikuo
Published: April 2008

ErbB3 receptor tyrosine kinase has been shown to induce tumor progression in several types of cancer through heterodimerization with ErbB2. However, the role of ErbB3 and its ligand heregulin (HRG) in tumor metastasis remains poorly understood. In the present study, we tried to clarify their contributions to the metastasis of ErbB3‐overexpressing B16‐BL6 melanoma cells. Stimulation with HRG induced phosphorylation of ErbB3 and metastatic properties including MMP‐9 expression, invasion, adhesion and experimental lung metastasis in vivo. These cellular responses were blocked by inhibiting the tyrosine kinase activity of EGFR with PD153035. In addition, phosphorylation of EGFR was rapidly induced by HRG, suggesting that EGFR is a possible heterodimeric counterpart of ErbB3. RNA interference demonstrated that subcutaneous tumor growth and angiogenesis was attenuated by inactivation of ErbB3 in cancer cells. Although experimental pulmonary metastasis was not affected by the knockdown of ErbB3, spontaneous metastasis was, even when primary tumors in the foot pad were amputated at a similar size. These results indicate that HRG‐induced activation of ErbB3 via EGFR promotes tumor growth and metastasis of melanoma cells. © 2008 Wiley‐Liss, Inc.
Persistent downregulation of the pancarcinoma‐associated epithelial cell adhesion molecule via active intranuclear methylation
Authors: van der Gun Bernardina T.F. , Wasserkort Reinhold , Monami Amélie , Jeltsch Albert , Raskó Tamás , Ślaska‐Kiss Krystyna , Cortese Rene , Rots Marianne G. , de Leij Lou F.M.H. , Ruiters Marcel H.J. , Kiss Antal , Weinhold Elmar , McLaughlin Pamela M.J.
Published: April 2008

The epithelial cell adhesion molecule (EpCAM) is expressed at high levels on the surface of most carcinoma cells. SiRNA silencing of EpCAM expression leads to reduced metastatic potential of tumor cells demonstrating its importance in oncogenesis and tumor progression. However, siRNA therapy requires either sequential delivery or integration into the host cell genome. Hence we set out to explore a more definite form to influence EpCAM gene expression. The mechanisms underlying the transcriptional activation of the EpCAM gene, both in normal epithelial tissue as well as in carcinogenesis, are poorly understood. We show that DNA methylation plays a crucial role in EpCAM expression, and moreover, active silencing of endogenous EpCAM via methylation of the EpCAM promoter results in a persistent downregulation of EpCAM expression. In a panel of carcinoma derived cell lines, bisulfite analyses showed a correlation between the methylation status of the EpCAM promoter and EpCAM expression. Treatment of EpCAM‐negative cell lines with a demethylating agent induced EpCAM expression, both on mRNA and protein level, and caused upregulation of EpCAM expression in an EpCAM‐positive cell line. After delivery of the DNA methyltransferase M.SssI into EpCAM‐positive ovarian carcinoma cells, methylation of the EpCAM promoter resulted in silencing of EpCAM expression. SiRNA‐mediated silencing remained for 4 days, after which EpCAM re‐expression increased in time, while M.SssI‐mediated downregulation of EpCAM maintained through successive cell divisions as the repression persisted for at least 17 days. This is the first study showing that active DNA methylation leads to sustained silencing of endogenous EpCAM expression. © 2008 Wiley‐Liss, Inc.
The risk of extra‐colonic, extra‐endometrial cancer in the Lynch syndrome
Authors: Watson Patrice , Vasen Hans F.A. , Mecklin Jukka‐Pekka , Bernstein Inge , Aarnio Markku , Järvinen Heikki J. , Myrhøj Torben , Sunde Lone , Wijnen Juul T. , Lynch Henry T.
Published: April 2008

Persons with the Lynch syndrome (LS) are at high risk for cancer, including cancers of the small bowel, stomach, upper urologic tract (renal pelvis and ureter), ovary, biliary tract and brain tumors, in addition to the more commonly observed colorectal and endometrial cancers. Cancer prevention strategies for these less common cancers require accurate, age‐specific risk estimation. We pooled data from 4 LS research centers in a retrospective cohort study, to produce absolute incidence estimates for these cancer types, and to evaluate several potential risk modifiers. After elimination of 135 persons missing crucial information, cohort included 6,041 members of 261 families with LS‐associated MLH1 or MSH2 mutations. All were either mutation carriers by test, probable mutation carriers (endometrial/colorectal cancer‐affected), or first‐degree relatives of these. Among mutation carriers and probable carriers, urologic tract cancer (N = 98) had an overall lifetime risk (to age 70) of 8.4% (95% CI: 6.6–10.8); risks were higher in males (p < 0.02) and members of MSH2 families (p < 0.0001). Ovarian cancer (N = 72) had an lifetime risk of 6.7% (95% CI: 5.3–9.1); risks were higher in women born after the median year of birth (p < 0.008) and in members of MSH2 families (p < 0.006). Brain tumors and cancers of the small bowel, stomach, breast and biliary tract were less common. Urologic tract cancer and ovarian cancer occur frequently enough in some LS subgroups to justify trials to evaluate promising prevention interventions. Other cancer types studied occur too infrequently to justify strenuous cancer control interventions. © 2008 Wiley‐Liss, Inc.
How basal are triple‐negative breast cancers?
Authors: Bertucci François , Finetti Pascal , Cervera Nathalie , Esterni Benjamin , Hermitte Fabienne , Viens Patrice , Birnbaum Daniel
Published: April 2008

The basal molecular subtype of breast cancer (BC) is defined by the mRNA expression pattern of an intrinsic ∼500‐gene set. It is the most homogeneous subtype in transcriptional terms, and one of the most aggressive in prognostic terms. Clinical trials testing new systemic therapeutic strategies have been launched in basal BCs. Although no proof of evidence has yet been reported, basal tumors are currently assimilated to and selected as triple‐negative (TN) BCs in these trials because of their frequent immunohistochemical (IHC) negativity for hormone and ERBB2 receptors. Here, we have assessed the degrees of correlation and of homogeneity of the TN phenotype (IHC‐based definition) and the basal subtype (gene expression‐based definition). We analyzed 172 TN BCs defined by gene expression profile as basal (123 cases) and nonbasal (49 cases). Conversely, 160 tumors were defined as basal by their gene expression profile and included 123 TN and 37 non‐TN samples. Uni‐ and multivariate analyses revealed that TN BCs represent a more heterogeneous group than basal BCs, including basal and nonbasal tumors very different both at the histoclinical and molecular level, notably for mRNA expression of molecules targeted by specific therapies under evaluation in clinical trials. These results call for caution in the interpretation of ongoing trials and selection of patients in future trials. They also warrant the identification of molecular markers for basal BCs more clinically applicable than gene expression profiles. © 2008 Wiley‐Liss, Inc.
Optimization of transglutaminase extraction produced by Bacillus circulans BL32 on solid‐state cultivation
Authors: de Souza Claucia Fernanda Volken , Rodrigues Rafael Costa , Heck Júlio Xandro , Ayub Marco Antônio Záchia
Published: April 2008

BACKGROUND: This paper reports investigations of the extraction of transglutaminase (TGase) produced by Bacillus circulans BL32 on solid‐state cultivation in order to obtain a crude extract with the highest possible specific activity. The optimization of downstream processing parameters for the effective recovery of the enzyme was carried out using response surface methodology based on the central composite rotatable design (CCRD) to reduce losses in the cultivated solids and to obtain a crude extract as concentrated as possible. Several solvents and temperatures were tested, followed by a 23 factorial design performed to optimize conditions extraction time, mechanical agitation, and solid:liquid ratio.

RESULTS: The mathematical model showed that solid:liquid ratio has a significant negative effect on transglutaminase recovery. The optimal conditions for extraction were: water as solvent at 7 °C; 5 min extraction time; agitation speed 250 rpm; and 1:6 solid:liquid ratio. Under these conditions the model predicts a maximum response of 0.291 U mg−1 of protein of transglutaminase activity recovery, very closely matching experimental activity of 0.285 U mg−1 of protein. TGase recovery achieved under the optimized extraction conditions, according to the CCRD, was 2.5‐fold higher than that obtained under non‐optimized conditions previously employed.

CONCLUSION: Results show that TGase can be produced in cheap solid state cultivations and the optimization of its downstream processing parameters can improve enzyme recovery in crude extracts and may have important impacts on enzyme costs. Copyright © 2008 Society of Chemical Industry
High resolution X‐ray phase contrast synchrotron imaging of normal and ligation damaged rat sciatic nerves
Authors: Kim Bong‐Il , Kim Ki‐Hong , Youn Hwa‐Shik , Jheon Sanghoon , Kim Jong‐Ki , Kim Hongtae
Published: April 2008

This study was performed to apply synchrotron radiation (SR) imaging to a neuropathologic evaluation technique after treatment of peripheral nerve blocks. A phase contrast synchrotron images of normal and ligation damaged rat sciatic nerve were obtained with an 8 KeV monochromatic beam and 20‐μm thick CsI(TI) scintillation crystal. The visual image was magnified using a 20× microscope objective and captured using an analog CCD camera. Obtained images were compared with conventional light microscopic findings from the same nerve samples. By using an edge enhancement effect of phase const with SR, we could easily discriminate each nerve fiber and identify the arrangement of nerve fibers within a whole thickness (about 1 mm in diameter) of peripheral nerve without sectioning and fixation. The composite SR image of a ligation damaged rat sciatic nerve sample showed that the response to nerve injury was different on each side of the site of injury. The SR image of damaged distal lesion showed destruction of neural microarchitecture and typical extensive Wallerian degeneration of nerve fibers as clearly as histologic image. We could get very detailed morphologic data for Wallerian degeneration of nerve fibers by using the SR imaging technique. We believe that the phase contrast synchrotron imaging has great potential as an imaging tool in the bioscience and medical science. Microsc. Res. Tech., 2008. © 2008 Wiley‐Liss, Inc.
Enrichment of eicosapentaenoic acid and docosahexaenoic acid from sardine by‐products by supercritical fluid fractionation
Authors: Létisse Marion , Comeau Louis
Published: April 2008

Based on the principle of supercritical chromatography, a fractionation process for fatty acid methyl esters (FAMEs) under supercritical conditions was studied with the aim of obtaining in extracts highly enriched eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish cannery waste. Yields of the fractionation process were enhanced by using adjuvant material and modifying CO2volumetric density and temperature. The combination of adjuvant properties with optimized pressure and temperature conditions permitted efficient fractionations of FAMEs, according to chain length and degree of unsaturation, in high purity (up to 95% of FAME) and good yields (45% of EPA and DHA starting potential). This work shows how green technologies, such as supercritical processes, can constitute a good alternative to the use of organic solvents in classical methods for valorisation of complex food industry waste.
Supercritical fluid extraction of polyhalogenated pollutants from aquaculture and marine environmental samples: A review
Authors: García‐Rodríguez Diego , Carro‐Díaz Antonia María , Lorenzo‐Ferreira Rosa Antonia
Published: April 2008

This article focuses on the state‐of‐the‐art in sample preparation using supercritical fluid extraction (SFE), to monitor the content of polyhalogenated pollutants in aquaculture and marine environmental samples. Marine sediments and biological applications, including several types of samples matrices (fish, shellfish, seaweed and fish feed) and analyte groups (polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), polybrominated diphenylethers (PBDEs), polychlorinated dibenzo‐p‐dioxin (PCDD)/Fs and organochlorinated pesticide (OCPs)) are discussed with respect to SFE use and optimisation of conditions. We also discuss the great analytical potential of SFE, the integration of the extraction and clean‐up steps for rapid sample processing justifying its use for routine work. The most recent SFE applications to the determination of these pollutants in marine environmental (biota and sediment) samples, published in the last 15 years, are reviewed.
Overview of the retention in subcritical fluid chromatography with varied polarity stationary phases
Authors: Lesellier Eric
Published: April 2008

Retention and separation of achiral compounds in supercritical fluid chromatography (SFC) depend on numerous parameters: some of these parameters are identical to those encountered in HPLC, such as the mobile phase polarity, while others are specific to SFC, as the density changes of the fluid, due to temperature and/or pressure variations. Additional effects are also related to the fluid compressibility, leading to unusual retention changes in SFC, for instance when flow rate or column length is varied. These additional effects can be minimised by working at lower temperatures in the subcritical domain, simplifying the understanding of retention behaviours. In these subcritical conditions, varied modifiers can be mixed to carbon dioxide, from hexane to methanol, allowing tuning the mobile phase polarity. With nonpolar modifiers, polar stationary phases are classically used. These chromatographic conditions are close to the ones of normal‐phase LC. The addition of polar modifiers such as methanol or ACN increases the mobile phase polarity, allowing working with less polar stationary phases. In this case, despite the absence of water, retention behaviours generally follow the rules of RP LC. Moreover, because identical mobile phases can be used with all stationary phase types, from polar silica to nonpolar C18‐bonded silica, the classical domains, RP and normal‐phase, are easily brought together in SFC. A unified classification method based on the solvation parameter model is proposed to compare the stationary phase properties used with the same subcritical mobile phase.
Nonexistence of local minima of supersolutions for the polyharmonic problems
Authors: Li Liangpan
Published: April 2008

In this note we study the nonexistence of local minima of the supersolutions of the polyharmonic equations on the balls under generalized homogeneous Dirichlet boundary conditions. Under suitable restriction on the dimensions, this means that a generalized clamped circular plate, which is pushed from below, cannot bend downwards even locally. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Positive solutions of non‐positone Dirichlet boundary value problems with singularities in the phase variables
Authors: Agarwal Ravi P. , O'Regan Donal , Staněk Svatoslav
Published: April 2008

The paper presents existence results for positive solutions of the differential equations x ″ + μh (x) = 0 and x ″ + μf (t, x) = 0 satisfying the Dirichlet boundary conditions. Here μ is a positive parameter and h and f are singular functions of non‐positone type. Examples are given to illustrate the main results. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Unique like everybody else? The dual role of consumers' need for uniqueness
Authors: Ruvio Ayalla
Published: April 2008

Uniqueness has a positive and attractive connotation, but being too unique can result in social sanctions. This paper focuses on the dual role of consumers' need for uniqueness. The findings of two studies in Israel support the notion that expressing uniqueness via consumption behavior is a safe way to achieve a different sense of being without damaging an individual's sense of social assimilation. The results imply a possible new theoretical view of the interplay between consumers' need for uniqueness and their need for social assimilation. © 2008 Wiley Periodicals, Inc.
An empirical investigation of framing effects in negotiations: A study of single‐family home sales
Authors: Witte Carl L. , Grünhagen Marko , Gentry James W.
Published: April 2008

This paper integrates Prospect Theory and the concept of framing in a study of consumer negotiated pricing in a real estate context. Building on previously conducted experimental designs, a field survey indicated that home sellers using sales price as a reference point display greater willingness to make concessions than those who use equity as their reference point. Further, the third‐party influence of the realtor was shown to alter Prospect Theory predictions so that even equity‐based sellers became concessionary. © 2008 Wiley Periodicals, Inc.
Test–retest repeatability of assessing environmental and lifestyle factors in Parkinson's disease
Authors: Yip Chun‐Wai , Tan Eng‐King
Published: April 2008

Epidemiological studies of environmental risk factors in Parkinson's disease (PD) are dependent on recollection of past exposures based on patients' self‐reports. There are limited studies that have assessed the quality of such data. We conducted a prospective study to determine the test–retest repeatability of environmental and lifestyle factors, and medical data in a PD cohort of Asian ethnicity. A total of 150 consecutive PD patients were initially screened, and 100 were recruited and completed an initial interview. Eighty‐three patients completed the second interview more than 6 months later. Lifestyle habits (such as smoking and coffee consumption) showed excellent agreement (κ > 0.90). For the amount and duration of coffee, tea, alcohol, and cigarette smoking exposure, the total agreement in the response for these factors in the repeat interview were noted in 71.4%, 73.3%, 100%, and 90%, respectively (ICC > 0.83). Medical conditions for which the patients were on treatment, such as diabetes, hypertension, and stroke, revealed very high repeatability (κ = 0.81–0.90). Environmental exposures like well‐water consumption and prior farm‐dwelling produced a moderately good repeatability (κ = 0.66–0.77). In conclusion, our study demonstrates that even over long interval period of more than half a year, self‐report lifestyle exposure information, personal and environmental exposure data can be collected with moderate‐to‐high repeatability from PD patients. © 2008 Movement Disorder Society