bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Exenatide in Patients With Type 2 Diabetes
Authors: Hood Robert , Valentine Virginia , Mac Susanna , Polonsky William H
Published: September 2006

Glucose homeostasis is regulated by a complex interplay of multiple hormones, including hormones from the pancreas (insulin, glucagon, and amylin)and the gut (glucagon-like peptide 1 [GLP-1] and glucose-dependent insulinotropic polypeptide). Most therapeutic options are focused on abnormal insulin secretion and signalling and do not address the role these other hormones play in glucoregulation and the diabetic state.

The inability to control glycemia over the long term utilizing single oral agents is reflected by the need to use various agents, alone or in combination, over time. In addition, the presence of associated side effects and clinical shortcomings of many therapies has prompted the search for new therapeutic agents that address the underlying dysregulation of multiple hormones found in people with diabetes. One of these agents, exenatide, mimics several of the actions of GLP-1 and is the first agent in a new class called incretin mimetics.

Exenatide was approved by the Food and Drug Administration in 2005 as an adjunctive therapy to metformin and/or sulfonylurea regimens for individuals with type 2 diabetes who have not achieved adequate glycemic control. Clinical trials indicate that subjects taking 10 μg of exenatide twice daily for 6 months had hemoglobin A1c (A1C) reductions of ∼1% and body weight reductions of ∼2 kg. After 1.5 years of exenatide treatment,reductions in A1C were sustained (1.1%), and body weight reductions were progressive (4.4 kg). In addition, exenatide treatment for 1.5 years resulted in improvements in some cardiovascular risk factors. For individuals with type 2 diabetes not achieving adequate glucose control with metformin and/or sulfonylureas, incretin mimetics such as exenatide may offer the opportunity for improved glycemic control with fewer clinical shortcomings than other available treatments.
Effects of Photo‐oxidation on the Performance of Poly[2‐methoxy‐5‐(3′,7′‐dimethyloctyloxy)‐1,4‐phenylene vinylene]:[6,6]‐Phenyl C61‐Butyric Acid Methyl Ester Solar Cells
Authors: Pacios R. , Chatten A. J. , Kawano K. , Durrant J. R. , Bradley D. D. C. , Nelson J.
Published: September 2006

A study of the photo‐oxidation of films of poly[2‐methoxy‐5‐(3′,7′‐dimethyloctyloxy)‐1,4‐phenylene vinylene] (MDMO‐PPV) blended with [6,6]‐phenyl C61‐butyric acid methyl ester (PCBM), and solar cells based thereon, is presented. Solar‐cell performance is degraded primarily through loss in short‐circuit current density, JSC. The effect of the same photodegradation treatment on the optical‐absorption, charge‐recombination, and charge‐transport properties of the active layer is studied. It is concluded that the loss in JSC is primarily due to a reduction in charge‐carrier mobility, owing to the creation of more deep traps in the polymer during photo‐oxidation. Recombination is slowed down by the degradation and cannot therefore explain the loss in photocurrent. Optical absorption is reduced by photo‐bleaching, but the size of this effect alone is insufficient to explain the loss in device photocurrent.
Controlled Encapsulation of Hydrophobic Liquids in Hydrophilic Polymer Nanofibers by Co‐electrospinning
Authors: Díaz J. E. , Barrero A. , Márquez M. , Loscertales I. G.
Published: September 2006

There are many technical situations, such as various biological or medical applications, in which a hydrophobic fluid must be encapsulated inside a hydrophilic polymer shell in the form of tiny microscopic pieces. A novel approach is presented, based on the co‐electrospinning of the hydrophilic polymer melt (outside) and the hydrophobic fluid (inside), which results in beaded micro‐ and nanofibers, such that the hydrophobic fluid is efficiently encapsulated inside the beads. For the selected fluid couple, the low liquid–liquid surface tension and the high viscosity of the melt prevent the varicose break‐up of inner fluid in the coaxial electrified jet until the very end of the co‐electrospinning process. The resulting fibers present beads filled with the hydrophobic fluid, separated by a rather uniform distance whose length depends partially on the melt flow rate. The bead diameter grows with the inner flow rate, going from a monosized to a bisized distribution. In the case under study, the maximum relative (inner‐to‐outer) flow rate is one. The diameter of the solid fibers between beads scales well with existing theories for simple electrospinning.
Intrinsic Dinitrogen Activation at Bare Metal Atoms
Authors: Himmel Hans‐Jörg , Reiher Markus
Published: September 2006

There is ongoing interest in metal complexes which bind dinitrogen and facilitate either its reduction or oxidation under mild conditions. In nature, the enzyme nitrogenase catalyzes this process, and dinitrogen fixation occurs under mild and ambient conditions at a metal–sulfur cluster in the center of the MoFe protein, but the mechanism of this process remains largely unknown. In the last few years, new important discoveries have been made in this field. In this review are discussed recent findings on the interaction of N2 with metal atoms and metal‐atom dimers from all groups of the periodic table as provided by gas‐phase as well as matrix‐isolation experiments. Intrinsic dinitrogen activation at such bare metal atoms is then related to corresponding processes at complexes, clusters, and surfaces.
Cover Picture: Contribution of Ligand Desolvation to Binding Thermodynamics in a Ligand–Protein Interaction (Angew. Chem. Int. Ed. 38/2006)
Authors: Shimokhina Natalia , Bronowska Agnieszka , Homans Steve W.
Published: September 2006

Ligand–protein interactions are associated with the desolvation of a ligand as it enters the protein‐binding pocket (see cover picture). Homans and co‐workers describe in their Communication on page 6374 ff. an estimate of the thermodynamic cost associated with this desolvation process. These data permit a complete breakdown of the binding thermodynamics into contributions from the ligand, protein, and solvent for the interaction of a small‐molecule ligand with the mouse major urinary protein.
Biologische Kampfstoffe: Nachweis und Bekämpfung: Strategien gegen Milzbrand, Pocken & Co.
Authors: Richardt André , Russman Heiko
Published: September 2006

Die Erreger von infektiösen Krankheiten können trotz internationaler Ächtung für kriminelle Zwecke missbraucht werden. Deshalb ist eine genaue Kenntnis der Detektion und der Dekontamination von biologischen Erregern für den militärischen und zivilen Katastrophenschutz von elementarem Interesse. Für die Detektion und Dekontamination dieser Erreger existiert eine Vielzahl unterschiedlicher Methoden. Der Detektion kommt dabei eine Schlüsselrolle zu. Je schneller und genauer bestimmt wird, um welchen Krankheitserreger es sich handelt, desto eher kann situationsbezogen reagiert und eine auf den jeweiligen Erreger abgestimmte Dekontaminationsmethode angewendet werden.
Warum wird das Blattgrün im Herbst abgebaut?
Authors: Krupinska Karin
Published: September 2006

Das Grün der Blätter wird durch komplex aufgebaute Farbstoffe, die Chlorophylle, verursacht. Während die Biosynthese der Chlorophylle bereits vor 20 Jahren in ihren wesentlichen Schritten aufgeklärt wurde, war die Biochemie ihres Abbaus bis vor kurzem unbekannt. Früher nahm man an, dass die Chlorophylle abgebaut werden, damit die Pflanze den darin enthaltenen Stickstoff zurückgewinnen kann – doch neue Forschungsergebnisse zeigen, dass der Abbau nicht zum Recycling, sondern zum Entgiften dient.
Sir Charles Scott Sherrington begründete die moderne Physiologie des Nervensystems
Authors: Penzlin Heinz
Published: September 2006

Vor hundert Jahren erschien das Buch “The integrative action of the nervous system”, mit dem Charles Scott Sherrington, der zu dieser Zeit als Professor für Physiologie an der Universität Liverpool lehrte und forschte, eine neue Epoche der neurobiologischen Forschung einleitete. Auf der Grundlage einer großen Anzahl von Laborversuchen entwickelte er eine Theorie der wechselseitigen Abhängigkeiten der Reflexaktivitäten, der reflexiven Erregung und Hemmung und damit der “integrativen Wirkung” des Nervensystems. Er erhielt im Jahre 1932 gemeinsam mit Edgar Douglas Adrian den Nobelpreis für Physiologie.
Investigation of Guanosine‐Quartet Assemblies by Vibrational and Electronic Circular Dichroism Spectroscopy, a Novel Approach for Studying Supramolecular Entities
Authors: Setnička Vladimír , Urbanová Marie , Volka Karel , Nampally Sreenivasachary , Lehn Jean‐Marie
Published: September 2006

The self‐assembly of guanosine‐5′‐hydrazideG‐1in D2O, in the presence and absence of sodium cations, has been investigated by chiroptical techniques: electronic (ECD) and the newly introduced vibrational (VCD) circular dichroism spectroscopy. Using a combination of ECD and VCD with other methods such as IR, electron microscopy, and electrospray ionization mass spectrometry (ESI‐MS) it was found thatG‐1produces long‐range chiral aggregates consisting of G‐quartets, (G‐1)4, subsequently stacked into columns, [(G‐1)4]n, induced by binding of metal cations between the (G‐1)4species. This process, accompanied by gelation of the sample, is highly efficient in the presence of an excess of sodium cations, leading to aggregates with strong quartet–quartet interaction. Thermally induced conformational changes and conformational stability of guanosine‐5′‐hydrazide assemblies were studied by chiroptical techniques and the melting temperature of the hydrogels formed was obtained. The temperature‐dependent experiments indicate that the long‐range supramolecular aggregates are dissociated by increasing temperature into less ordered species, monomers, or other intermediates in equilibrium, as indicated by MS experiments.
Olefin Epoxidation with Hydrogen Peroxide Catalyzed by Lacunary Polyoxometalate [γ‐SiW10O34(H2O)2]4−
Authors: Kamata Keigo , Kotani Miyuki , Yamaguchi Kazuya , Hikichi Shiro , Mizuno Noritaka
Published: September 2006

The tetra‐n‐butylammonium (TBA) salt of the divacant Keggin‐type polyoxometalate [TBA]4[γ‐SiW10O34(H2O)2] (I) catalyzes the oxygen‐transfer reactions of olefins, allylic alcohols, and sulfides with 30 % aqueous hydrogen peroxide. The negative Hammett ρ+ (−0.99) for the competitive oxidation of p‐substituted styrenes and the low value of (nucleophilic oxidation)/(total oxidation), XSO=0.04, for I‐catalyzed oxidation of thianthrene 5‐oxide (SSO) reveals that a strongly electrophilic oxidant species is formed on I. The preferential formation of trans‐epoxide during epoxidation of 3‐methyl‐1‐cyclohexene demonstrates the steric constraints of the active site of I. The I‐catalyzed epoxidation proceeds with an induction period that disappears upon treatment of I with hydrogen peroxide. 29Si and 183W NMR spectroscopy and CSI mass spectrometry show that reaction of I with excess hydrogen peroxide leads to fast formation of a diperoxo species, [TBA]4[γ‐SiW10O32(O2)2] (II), with retention of a γ‐Keggin type structure. Whereas the isolated compound II is inactive for stoichiometric epoxidation of cyclooctene, epoxidation with II does proceed in the presence of hydrogen peroxide. The reaction of II with hydrogen peroxide would form a reactive species (III), and this step corresponds to the induction period observed in the catalytic epoxidation. The steric and electronic characters of III are the same as those for the catalytic epoxidation by I. Kinetic, spectroscopic, and mechanistic investigations show that the present epoxidation proceeds via III.
Cytoskeletal asymmetry in Zea mays subsidiary cell mother cells: A monopolar prophase microtubule half‐spindle anchors the nucleus to its polar position
Authors: Panteris Emmanuel , Apostolakos Panagiotis , Galatis Basil
Published: September 2006

Double labeling of microtubules and actin filaments revealed that in prophase subsidiary mother cells of Zea mays a monopolar prophase microtubule “half‐spindle” is formed, which lines the nuclear hemisphere distal to the inducing guard mother cell. The nuclear hemisphere proximal to the guard mother cell is lined by an F‐actin cap, consisting of a cortical F‐actin patch and actin filaments originating from it. The microtubules of the “half‐spindle” decline from the nuclear surface and terminate to the preprophase microtubule band. After disintegration of the latter, a bipolar metaphase spindle is organized. The polar F‐actin cap persists during mitosis and early cytokinesis, extending to the chromosomes and the subsidiary cell daughter nucleus. In oryzalin treated subsidiary mother cells the prophase nuclei move away from the polar site. Cytochalasin B and latrunculin‐B block the polar migration of subsidiary mother cell nuclei, but do not affect those already settled to the polar position. The prophase nuclei of latrunculin‐B treated subsidiary mother cells are globally surrounded by microtubules, while the division plane of latrunculin‐B treated subsidiary mother cells is misaligned. The prophase nuclei of brick 1 mutant Zea mays subsidiary mother cells without F‐actin patch are also globally surrounded by microtubules. The presented data show that the prophase microtubule “half‐spindle”‐preprophase band complex anchors the subsidiary mother cell nucleus to the polar cell site, while the polar F‐actin cap stabilizes the one metaphase spindle pole proximal to the inducing guard mother cell. Cell Motil. Cytoskeleton 2006. © 2006 Wiley‐Liss, Inc.
Assembling microtubules disintegrate the postsynaptic density in vitro
Authors: Lo Li‐Ping , Liu Szu‐Heng , Chang Yen‐Chung
Published: September 2006

The postsynaptic density (PSD), a disk‐shaped protein aggregation of several hundred nm in diameter, plays important roles in the signal transduction and molecular organization of the excitatory synapses in mammalian CNS. The PSD resides in the microfilament‐enriched cytoplasm of dendritic spines where the transient appearance of microtubules has been reported. When PSD isolated from porcine brain was incubated with polymerizing α,β‐tubulins, its turbidity became greater than that of the original PSD, suggesting that the PSD's structure was altered upon incubating with assembling microtubules. By transmission electron microscopy, smaller PSD fragments and several novel structures, including holes and finger‐like extensions, were found in the PSD after incubation with assembling microtubules, but not in the original PSD or in the PSD incubated with α,β‐tubulins pretreated with vincristine. The results suggest that the interactions with assembling microtubules may result in the formation of holes in the PSD, and the rupture of these holes subsequently leads to the formation of smaller PSD fragments. Cell Motil. Cytoskeleton 2006. © 2006 Wiley‐Liss, Inc.
Carbohydrates as Scaffolds in Drug Discovery
Authors: Meutermans Wim , Le Giang Thanh , Becker Bernd
Published: September 2006

Drug discovery has long suffered from the difficulty of having to place pharmacophoric groups in just the right spatial arrangement to elicit the desired biological response. Although some molecule classes have been discovered that seem to be privileged structures for at least some drug–receptor interactions, there remains the challenge to design and synthesize molecules with high specific affinity to pharmacologically important targets. With their high density of stereochemical information and their relative rigidity, carbohydrates provide excellent platforms upon which to display a number of substituents in a sterically defined way, hence offering the opportunity to harness their unique features for the drug‐discovery process. This review highlights the progress that has been made in the development of carbohydrate scaffolds for drug discovery.
Phosphorylated 4E binding protein 1: A hallmark of cell signaling that correlates with survival in ovarian cancer
Authors: Castellvi Josep , Garcia Angel , Rojo Federico , Ruiz‐Marcellan Carmen , Gil Antonio , Baselga Jose , Ramon y Cajal Santiago
Published: September 2006

BACKGROUND.

Growth factor receptors and cell signaling factors play a crucial role in human carcinomas and have been studied in ovarian tumors with varying results. Cell signaling involves multiple pathways and a myriad of factors that can be mutated or amplified. Cell signaling is driven through the mammalian target of rapamycin (mTOR) and extracellular regulated kinase (ERK) pathways and by some downstream molecules, such as 4E binding protein 1 (4EBP1), eukaryotic initiation factor 4E, and p70 ribosomal protein S6 kinase (p70S6K). The objectives of this study were to analyze the real role that these pathways play in ovarian cancer, to correlate them with clinicopathologic characteristics, and to identify the factors that transmit individual proliferation signals and are associated with pathologic grade and prognosis, regardless specific oncogenic alterations upstream.

METHODS.

One hundred twenty‐nine ovarian epithelial tumors were studied, including 20 serous cystadenomas, 7 mucinous cystadenomas, 11 serous borderline tumors, 16 mucinous borderline tumors, 29 serous carcinomas, 16 endometrioid carcinomas, 15 clear cell carcinomas, and 15 mucinous carcinomas. Tissue microarrays were constructed, and immunohistochemistry for the receptors epidermal growth factor receptor (EGFR) and c‐erb‐B2 was performed and with phosphorylated antibodies for protein kinase B (AKT), 4EBP1, p70S6K, S6, and ERK.

RESULTS.

Among 129 ovarian neoplasms, 17.8% were positive for c‐erb‐B2, 9.3% were positive for EGFR, 47.3% were positive for phosphorylated AKT (p‐AKT), 58.9% were positive for p‐ERK, 41.1% were positive for p‐4EBP1, 26.4% were positive for p70S6K, and 15.5% were positive for p‐S6. Although EGFR, p‐AKT, and p‐ERK expression did not differ between benign, borderline, or malignant tumors, c‐erb‐B2, p‐4EBP1, p‐p70S6K, and p‐S6 were expressed significantly more often in malignant tumors. Only p‐4EBP1 expression demonstrated prognostic significance (P = .005), and only surgical stage and p‐4EBP1 expression had statistical significance in the multivariate analysis.

CONCLUSIONS.

In patients with ovarian carcinoma, significant expression of p‐4EBP1 was associated with high‐grade tumors and a poor prognosis, regardless other oncogenic alterations upstream. This finding supports the study of this factor as a hallmark or pivotal factor in cell signaling in ovarian carcinoma that may crucial in the transmission of the proliferation cell signal and may reflect the real oncogenic role of this pathway in ovarian tumors. Cancer 2006. © 2006 American Cancer Society.
Early effects of imatinib mesylate on the expression of insulin‐like growth factor binding protein‐3 and positron emission tomography in patients with gastrointestinal stromal tumor
Authors: Trent Jonathan C. , Ramdas Latha , Dupart Jheri , Hunt Kelly , Macapinlac Homer , Taylor Ellen , Hu Limei , Salvado August , Abbruzzese James L. , Pollock Raphael , Benjamin Robert S. , Zhang Wei
Published: September 2006

BACKGROUND.

Imatinib has demonstrated marked clinical efficacy against gastrointestinal stromal tumor (GIST). Microarray technology, real‐time polymerase chain reaction (PCR) validation, and fluorodeoxyglucose‐positron emission tomography (FDG‐PET) imaging were used to study the early molecular effects of imatinib antitumor activity in GIST.

METHODS.

After exposure of sensitive and resistant sarcoma cell lines to imatinib for 24 to 48 hours, the changes in gene expression were evaluated using a 1146 unique pathway array with Western blot validation. Real‐time PCR was used to confirm changes in gene expression in human GIST samples (preimatinib biopsy and postimatinib surgical specimen after 3–7 days of therapy). FDG‐PET was performed to correlate radiographic findings with the effects of imatinib on gene expression in GIST.

RESULTS.

In all, 55 genes demonstrated a ≥ 2‐fold change after imatinib treatment of the GIST882 cells. Among these genes there was up‐regulation of insulin‐like growth factor binding protein‐3 (IGFBP‐3), a protein that modulates proliferation and apoptosis. Western blot analysis confirmed the increase of IGFBP‐3 only in imatinib‐sensitive GIST882 cells. Up to a 7‐fold induction (49% mean increase; P = .08) of IGFBP‐3 mRNA was found in tumor samples from patients with low residual FDG uptake, whereas there was an up to 12‐fold reduction (−102% mean decrease; P = .03) in IGFBP‐3 in those patients with high residual FDG uptake after imatinib therapy.

CONCLUSIONS.

In the current study, imatinib appears to regulate numerous genes and specifically induces IGFBP‐3 in GIST cells and tumor samples. IGFBP‐3 levels also were found to be inversely correlated with residual FDG uptake in GIST patients early in imatinib therapy. These initial observations suggest that IGFBP‐3 is an important early marker of antitumor activity of imatinib in GIST. Cancer 2006. © 2006 American Cancer Society.
Analysis of thick functionally graded plates by local integral equation method
Authors: Sladek J. , Sladek V. , Hellmich Ch. , Eberhardsteiner J.
Published: September 2006

Analysis of functionally graded plates under static and dynamic loads is presented by the meshless local Petrov–Galerkin (MLPG) method. Plate bending problem is described by Reissner–Mindlin theory. Both isotropic and orthotropic material properties are considered in the analysis. A weak formulation for the set of governing equations in the Reissner–Mindlin theory with a unit test function is transformed into local integral equations considered on local subdomains in the mean surface of the plate. Nodal points are randomly spread on this surface and each node is surrounded by a circular subdomain, rendering integrals which can be simply evaluated. The meshless approximation based on the moving least‐squares (MLS) method is employed in the numerical implementation. Numerical results for simply supported and clamped plates are presented. Copyright © 2006 John Wiley & Sons, Ltd.
Some techniques for avoiding dips of antenna radiation efficiency on improved Wheeler method
Authors: Ishii Nozomu , Kaneko Takayuki , Miyakawa Michio
Published: September 2006

When the efficiency of a monopole is measured by determining the radiation efficiency of a small antenna based on a waveguide and a movable short, there are dips at certain frequencies. In this paper, a transmission line model considering the loss in the movable short is introduced and the efficiency dip phenomena are explained. A method for avoiding the dip is presented. When two movable shorts on the left and right inserted into the waveguide are moved, an efficiency dip occurs at the resonant frequency of the cavity. Therefore, the movable range of the two movable shorts that will avoid the efficiency dip is investigated. When one of the movable shorts is fixed at an arbitrary location, there is a dip in the radiation efficiency at a specific frequency. Therefore, it is confirmed that the dip can be avoided by limiting the range of the fixed location of the movable short. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 90(1): 35–44, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.20323
Peripheral B cell receptor editing may promote the production of high‐affinity autoantibodies in CD22‐deficient mice
Authors: Yarkoni Yuval , Fischel Ruth , Kat Inbal , Yachimovich‐Cohen Nurit , Eilat Dan
Published: September 2006

CD22‐deficient mice are characterized by B cell hyperactivity and autoimmunity. We have constructed knock‐in CD22–/– mice, expressing an anti‐DNA heavy (H) chain (D42), alone or combined with Vκ1‐Jκ1 or Vκ8‐Jκ5 light (L) chains. The Ig‐targeted mice produced a lupus‐like serology that was age‐ and sex‐dependent. High‐affinity IgG autoantibodies were largely dependent on the selection of B cells with a particular H/L combination, in which a non‐transgenic, endogenous L chain was assembled by secondary rearrangements through the mechanism of receptor editing. Moreover, we present evidence that these secondary rearrangements are very prominent in splenic peripheral B cells. Since CD22 is primarily expressed on the surface of peripheral B cells, we propose a model for the development of a lupus‐like autoimmune disease by a combination of peripheral receptor editing and abnormal B cell activation.
Data augmentation for a Bayesian spatial model involving censored observations
Authors: Fridley Brooke L. , Dixon Philip
Published: September 2006

Spatial environmental data sometimes include below detection limit observations (i.e., censored values reported as less than a level of detection). Historically, the most common practice for analysis of such data has been to replace the censored observations with some function of the level of detection (LOD), like LOD/2. We show that estimates and standard errors found using this single substitution method are biased. In particular, the spatial variance and variability in estimation is underestimated. We develop a measurement error Bayesian spatial model for the analysis of spatial data with censored values. Parameter estimation and predictions at observed and unobserved locations are computed using a data augmentation (DA) method and Markov chain Monte Carlo (MCMC) algorithm. The DA method is illustrated using data from a dioxin contaminated site in Missouri. We also use simulation to investigate the small sample properties of predictions and parameter estimates and the robustness of the DA method. Copyright © 2006 John Wiley & Sons, Ltd.
Active caspase‐3 is required for osteoclast differentiation
Authors: Szymczyk K.H. , Freeman T.A. , Adams C.S. , Srinivas V. , Steinbeck M.J.
Published: September 2006

Based on our earlier observation that caspase‐3 is present in osteoclasts that are not undergoing apoptosis, we investigated the role of this protein in the differentiation of primary osteoclasts and RAW264.7 cells (Szymczyk KH, et al., 2005, Caspase‐3 activity is necessary for RANKL‐induced osteoclast differentiation. The Proceedings of the 8th ICCBMT). We noted that osteoclast numbers are decreased in long bones of procaspase‐3 knockout mice and that receptor activator of NF‐κB ligand (RANKL) does not promote differentiation of isolated preosteoclasts. In addition, after treatment with inhibitors of caspase‐3 activity, neither the wild‐type primary nor the RAW264.7 cells express TRAP or became multinucleated. We found that immediately following RANKL treatment, procaspase‐3 is cleaved and the activated protein is localized to lipid regions of the plasma membrane and the cytosol. We developed RAW264.7 procaspase‐3 knockdown clonal cell lines using RNAi technology. Again, treatment with RANKL fails to induce TRAP activity or multinucleation. Finally, we evaluated NF‐κB in procaspase‐3 silenced cells. We found that RANKL treatment prevented activation and nuclear translocation of NF‐κB. Together these findings provide direct support for the hypothesis that caspase‐3 activity is required for osteoclast differentiation. J. Cell. Physiol. 209: 836–844, 2006. © 2006 Wiley‐Liss, Inc.
Alterations in intranuclear localization of Runx2 affect biological activity
Authors: Zaidi Sayyed K. , Javed Amjad , Pratap Jitesh , Schroeder Tania M. , Westendorf Jennifer J. , Lian Jane B. , van Wijnen Andre J. , Stein Gary S. , Stein Janet L.
Published: September 2006

The transcription factor Runx2 controls osteoblast proliferation and differentiation. Runx2 organizes and assembles gene‐regulatory complexes in nuclear microenvironments where target genes are activated or suppressed in a context‐dependent manner. Intranuclear localization of Runx2 is mediated by the nuclear matrix‐targeting signal (NMTS), an autonomous motif with a loop (L1)‐turn‐loop (L2) structure that forms predicted protein–protein interaction surfaces. Here we examined the functional consequences of introducing mutations in the L1 and L2 loops of the NMTS. These mutant proteins enter the nucleus, interact with the hetero‐dimeric partner Cbfβ, and bind to DNA in vitro and in vivo. In addition, these mutants retain interaction with the carboxy‐terminus interacting co‐regulatory proteins that include TLE, YAP, and Smads. However, two critical mutations in the L2 domain of the NMTS decrease association of Runx2 with the nuclear matrix. These subnuclear targeting defective (STD) mutants of Runx2 compromise target gene activation or repression. The biological significance of these findings is reflected by decreased osteogenic differentiation of mesenchymal progenitors, concomitant with major changes in gene expression profiles, upon expression of the STD Runx2 mutant. Our results demonstrate that fidelity of temporal and spatial localization of Runx2 within the nucleus is functionally linked with biological activity. J. Cell. Physiol. 209: 935–942, 2006. © 2006 Wiley‐Liss, Inc.
Myogenic differentiation of dermal papilla cells from bovine skin
Authors: Rufaut N.W. , Goldthorpe N.T. , Wildermoth J.E. , Wallace O.A.M.
Published: September 2006

Cells from the dermal papilla and dermal sheath of hair follicles exhibit pronounced plasticity in vitro, being capable of adopting fat, bone, hematopoietic, and nerve cell phenotypes. In this study, we show that bovine dermal papilla cells (DPC) are also capable of undergoing skeletal muscle differentiation. DiI labeled DPC incorporated into myotubes when co‐cultured with differentiating C2C12 myoblasts. Bovine‐specific PCR assays showed that the muscle markers MyoD and myogenin were up‐regulated, confirming that the DPC had adopted a myogenic gene expression program. Nine clonal lines of DPC underwent both adipogenic and myogenic differentiation, demonstrating the multipotency of individual cells. Primary populations of both DPC and extra‐follicular dermal fibroblasts were also capable of both adipogenic and myogenic differentiation. However, on myogenic differentiation, cells derived from dermal papillae expressed higher levels of myogenin than primary fibroblasts derived from extra‐follicular dermis, suggesting that papilla cells undergo myogenesis more efficiently. This result shows that populations of fibroblastic cells derived from different anatomical sites within the skin are not equivalent with respect to their plasticity. Cultured DPC and dermal fibroblasts both expressed Pax3, a marker for the dermomyotome which represents a common embryological origin of muscle and dermis. Quantitative PCR showed that Pax3 expression levels before myogenic induction correlated with myogenin expression levels after myogenesis. These results suggest that a degree of dedifferentiation may underlie the plasticity of dermal cells in vitro, and that this plasticity may be predicted, at least in part, by levels of Pax3 expression. J. Cell. Physiol. 209: 959–968, 2006. © 2006 Wiley‐Liss, Inc.
Death receptor‐3 mediates apoptosis in human osteoblasts under narrowly regulated conditions
Authors: Borysenko Christopher W. , García‐Palacios Verónica , Griswold Reed D. , Li Yanan , Iyer Anand Krishnan V. , Yaroslavskiy Beatrice B. , Sharrow Allison C. , Blair Harry C.
Published: September 2006

We previously reported that a soluble form of the TNF‐family receptor death receptor‐3 (DR3) is expressed in osteoblasts. DR3 regulates death or differentiation in other tissues, and DR3 ligands occur in bone, but the function of DR3 in the osteoblast was unknown. We studied the expression of DR3 and the effects crosslinking antibodies to DR3 or of natural DR3 ligands in human osteoblasts. Western analysis showed that nontransformed osteoblasts and the MG63 osteosarcoma cell line produce both soluble decoy receptor and transmembrane isoforms of DR3. Cell surface labeling showed that low and high DR3‐expressing osteoblast populations occur. Verification of by cloning showed a point mutation in DR3 from MG63 cells. Activation of DR3 by antibody crosslinking or with DR3 ligands caused apoptosis in osteoblasts and in MG63 cells, but only in low‐density cell cultures. In dense cultures apoptosis did not occur, but nuclear factor‐κB nuclear translocation was observed under some conditions. Crosslinking of DR3 in high‐density MG63 cultures blocked expression of bone matrix elements. DR3 activation in high‐density nontransformed osteoblasts had only minor effects on cell maturation. We conclude that DR3 activation can mediate apoptosis in osteoblasts. Its activity is, however, highly restricted by its soluble ligand‐binding isoform and possibly also by alternate survival signals. In the presence of survival signals, DR3 may affect cell maturation although effects on differentiation were clearly seen only in the MG63 transformed cell line. J. Cell. Physiol. 209: 1021–1028, 2006. © 2006 Wiley‐Liss, Inc.
Development of a membrane‐aerated biofilm reactor to completely mineralise perchloroethylene in wastewaters
Authors: Ohandja D Guy , Stuckey David C
Published: September 2006

The feasibility of perchloroethylene (PCE) biodegradation using hybrid aerobic/anaerobic microcosms was investigated. Four main factors were evaluated in batch studies; the type of the electron donor, the nature of the inoculum, the effect of different concentrations of electron donor, and the effect of addition of different concentrations of oxygen. Results from these studies showed that; glucose was the best electron donor for PCE degradation, serum bottles seeded with acclimated biomass performed better than those seeded with the unacclimated biomass, glucose in excess did not improve PCE degradation, and the addition of pure oxygen significantly enhanced degradation. It was observed that serum bottles with acclimated sludge receiving oxygen achieved complete mineralisation of PCE to ethylene with mineralisation rates of 0.27 mg L−1 mg cells−1 h−1. Following these results a membrane‐aerated biofilm reactor (MABR) was constructed, and the batch degradation of 5.5 mg L−1 of PCE was followed for 44 days and PCE was completely removed from the system. The appearance of intermediate compounds proved that PCE was degraded, but not completely stripped out from the system. Degradation was not complete as some bio‐products were still found in the effluent, but there was no accumulation of a particular intermediate compound. The PCE removal rate observed in this MABR was 0.24 mg L−1 h−1. During the study on the effect of adding different concentrations of oxygen, a mass balance based on chloride in the bottles revealed that, 92–95% of the PCE could be accounted for, while only 60–65% of the PCE fed in the reactor could be accounted for as chloride. The MABR developed here may prove to have considerable potential in treating wastewater containing a variety of refractory organics such as PCE. Copyright © 2006 Society of Chemical Industry
Can you trust your cryostat? Reproducibility of cryostat section thickness
Authors: De Witt Hamer Philip C. , Bleeker Fonnet E. , Zwinderman Aeilko H. , Van Noorden Cornelis J.F.
Published: September 2006

Reproducibility of cryostat section thickness is required for valid quantitative microscopy. This is generally pursued by motorized sectioning using a low but constant speed. The purpose of our study was to compare variation in section thickness between motorized and manual cryostat sectioning. Serial sections were cut from a frozen block of homogenized tissue on different days. Lactate dehydrogenase activity was histochemically detected and calibrated absorbance measurements were taken. The coefficients of variation of measurements was 9.7% for motorized sectioning and 3.3% for manual sectioning. In conclusion, section thickness is similarly reproducible after manual sectioning compared with motorized sectioning, if not better. Microsc. Res. Tech., 2006. © 2006 Wiley‐Liss, Inc.
Q‐FIHC: Quantification of fluorescence immunohistochemistry to analyse p63 isoforms and cell cycle phases in human limbal stem cells
Authors: Di Iorio Enzo , Barbaro Vanessa , Ferrari Stefano , Ortolani Claudio , De Luca Michele , Pellegrini Graziella
Published: September 2006

Fluorescence microscopy has long been used for qualitative characterization of various parameters such as subcellular distribution of proteins, lipids, nucleic acids, and ions. However, quantification of these parameters is complicated by a variety of optical, biological, and physical factors. In the last decade, the progress achieved with powerful softwares and digital image processing systems has facilitated the development of fluorescence immunohistochemistry (FIHC) into a widely used quantitative assay (quantitative‐FIHC or Q‐FIHC). We describe here a rapid and sensitive Q‐FIHC assay based on the use of a laser scanning confocal microscope and advanced image analysis softwares (Zeiss semi automatic LSM 510 and fully automatic Axiovision 4.4) for the detection and quantification of fluorescent intensity in human corneal tissues and cells obtained from small clinical samples. We have used this methodology to characterize and quantify the gene expression profile of p63 and its ΔNα isoform, specific markers of human limbal stem cells. The validity of this method was evaluated through comparative studies with conventional approaches suggesting no significant differences and providing an alternative technique to traditional methods. Since Q‐FIHC requires at least 20‐fold less cells than traditional techniques, we have adopted it as the main quality control for our limbal cultures destined to clinical application. Microsc. Res. Tech., 2006. © 2006 Wiley‐Liss, Inc.
Effects of transcutaneous electrical nerve stimulation on motor cortex excitability in writer's cramp: Neurophysiological and clinical correlations
Authors: Tinazzi Michele , Zarattini Stefano , Valeriani Massimiliano , Stanzani Clementina , Moretto Giuseppe , Smania Nicola , Fiaschi Antonio , Abbruzzese Giovanni
Published: September 2006

We recently reported that transcutaneous electrical nerve stimulation (TENS) applied over forearm flexor muscles, a paradigm producing in physiological conditions transient changes in corticomotoneuronal excitability of forearm muscles, may improve motor symptoms in writer's cramp (WC). In the present study, we explored the possibility that one or repeated sessions of TENS might have beneficial effects on handwriting in WC by remodulating cortical excitability of forearm agonist and antagonist muscles. Motor evoked potentials (MEPs) after transcranial magnetic stimulation of the left motor cortex were recorded from the right flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles, before and after 1 and 15 sessions of TENS applied over flexor muscles in patients and in a control group. One session of TENS induced a significant smaller reduction of MEPs from the FCR and a smaller increase of the MEPs from the ECR in patients than in normal subjects. In WC, repeated sessions of TENS had the effect to decrease MEP amplitude in the FCR and to increase it in the ECR. This modulation was paralleled by a handwriting improvement. In conclusion, repeated TENS sessions may have the effect to re‐modulate excitability of the motor cortex in WC and this modulation might partially play a role in temporarily improving the handwriting. © 2006 Movement Disorder Society
Intravesical glucidic capsaicin versus glucidic solvent in neurogenic detrusor overactivity: A double blind controlled randomized study
Authors: de Sèze Marianne , Gallien Philippe , Denys Pierre , Labat Jean‐Jacques , Serment Gérard , Grise Philippe , Salle Jean‐Yves , Blazejewski Sylvie , Hazane Cécile , Moore Nicholas , Joseph Pierre‐Alain
Published: September 2006

Aims

Many studies report the use of alcoholic capsaicin instillation to treat neurogenic detrusor overactivity (NDO) in spinal cord injured (SCI) and multiple sclerosis (MS) patients. However, poor tolerability due to the irritative effect of the ethanol solvent limits its use. Our study aimed to evaluate the efficacy and tolerability of a new formulation of capsaicin in a glucidic solution in a multicenter clinical trial.

Materials and Methods

Thirty‐three patients (26MS/7SCI) suffering from urinary incontinence due to refractory NDO were prospectively enrolled in a double‐blind placebo controlled study and randomized to capsaicin group (CG, N = 17) or solvent group (SG, N = 16). They respectively received an intravesical instillation of 100 ml capsaicin diluted in glucidic solvent (CG) or glucidic solvent alone (SG). Efficacy (voiding chart, maximum cystometric capacity (MCC)) and tolerability were evaluated on days 0 (D0), 30 and 90.

Results

On D0, groups were homogeneous. On D30, significant improvement of overactive bladder syndrome and an increase in MCC were shown in CG, whereas there were no improvement in SG. No significant improvement was shown on D90 in both groups. There were no significant differences between groups regarding prevalence, duration, or intensity of side effects, except for short duration pubic pain during instillation more often reported in CG (58.8%) than in SG (12.5%) (P < 0.01).

Conclusion

This placebo controlled study using glucidic capsaicin confirms its short‐term efficacy in NDO patients. Global tolerance of glucidic capsaicin appeared satisfactory. Long‐term efficacy and tolerance of repeated glucidic capsaicin instillations need to be evaluated. Neurourol. Urodynam. 25:752–757, 2006. © 2006 Wiley‐Liss, Inc.
A pilot phase II study of alternate day ganciclovir and foscarnet in preventing cytomegalovirus (CMV) infections in at‐risk pediatric and adolescent allogeneic stem cell transplant recipients
Authors: Shereck Evan B. , Cooney Erin , van de Ven Carmella , Della‐Lotta Phyllis , Cairo Mitchell S.
Published: September 2006

Background

Prophylaxis with ganciclovir or foscarnet post allogeneic stem cell transplant (AlloSCT) reduces cytomegalovirus (CMV) disease. Combination ganciclovir/foscarnet is more effective than monotherapy in HIV patients with CMV retinitis. We hypothesized that alternate day ganciclovir and foscarnet for the prevention of CMV during the first 100 days after AlloSCT would be safe and effective.

Procedure

Fifty‐three pediatric and adolescent AlloSCT recipients receiving 57 AlloSCTs where donors and/or recipients were CMV seropositive received ganciclovir (5 mg/kg/48 hr) alternating with foscarnet (90 mg/kg/48 hr) from myeloid recovery (≥ANC 750/mm3) until Day +100.

Results

Patients were: M:F 31:22; age 6 years (0.8–18 years); donor sources: 25 related peripheral blood/bone marrow, 3 unrelated adult peripheral blood, 26 unrelated cord blood, and 3 related cord blood. GVHD prophylaxis included tacrolimus/mycophenolate mofetil (MMF). Median‐nucleated and CD34 cell counts were 7.3 × 108/kg and 5.07 × 106/kg, respectively, for BM/PBSC; 4.07 × 107/kg and 1.69 × 105/kg, respectively, for CB. Despite a 36.5% probability of Grades II–IV acute GVHD, no patient developed systemic CMV disease. Five percent had Grade IV hematological toxicity that required discontinuation of ganciclovir. Twenty‐five percent required discontinuation of foscarnet secondary to electrolyte abnormalities and/or renal dysfunction that were presumed to be multifactorial in origin. Probability of 1‐year overall survival was 58.8%.

Conclusions

Alternate day ganciclovir/foscarnet in AlloSCT recipients where recipient and/or donor is seropositive appears to be tolerable and 100% effective in preventing CMV systemic disease. A randomized study will be required to determine if this approach is superior to other CMV prophylactic designs. Pediatr Blood Cancer 2007;49:306–312. © 2006 Wiley‐Liss, Inc.
Treatment of Pediatric non‐Hodgkin lymphomas in a country with limited resources: Results of the first national protocol in Nicaragua
Authors: Baez F. , Pillon M. , Manfredini L. , Ocampo E. , Mendez G. , Ortiz R. , Palacios R. , Gutierrez T. , Tridello G. , Conter V. , Valsecchi MG. , Bellani F. Fossati , Cavalli F. , Masera G. , Rosolen A.
Published: September 2006

We report the results of a protocol for the diagnosis and treatment of pediatric non‐Hodgkin lymphomas (NHL) conducted in Nicaragua in the context of an international collaborative program. Fifty‐three children with NHL treated between 1996 and 2003 were retrospectively evaluated. Therapy was designed based on local drug availability and affordability with dose and schedule adaptations for Burkitt and lymphoblastic lymphomas. With a median follow‐up of 3 years, the projected 9‐year overall survival was 63% and event‐free survival 53%. The treatment was efficacious, feasible, and well tolerated in spite of the local socio‐economical conditions. Pediatr Blood Cancer 2008;50:148–152. © 2006 Wiley‐Liss, Inc.
Rovibrationally averaged properties of H2 using Monte Carlo methods
Authors: Alexander S. A. , Coldwell R. L.
Published: September 2006

Using variational Monte Carlo and a simple explicitly correlated wave function, we have computed 18 molecular properties of the hydrogen molecule (X1∑) at 24 internuclear distances. These properties have been combined with rapidly convergent rovibrational wave functions to produce rovibrationally averaged properties for several of the lowest rotational and vibrational levels of this system. Our results are in very good agreement with previous values found in the literature. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006
Temperature‐dependent conformational analysis of cyclononane: An ab initio study
Authors: Franco Mauro L. , Ferreira Dalva E. C. , Dos Santos Hélio F. , De Almeida Wagner B.
Published: September 2006

Quantum chemical methods were used for the theoretical determination of the conformational population for the relevant conformers of cyclononane, i.e., TBC, TCB, TCC, and M4 (or C1), which have been previously investigated experimentally through detailed examination of the nuclear magnetic resonance (NMR) spectrum. Our best Gibbs free energy result, evaluated with MP4(SDTQ)/6‐31G(d,p)//MP2/6‐31G(d,p) energy differences and MP2/6‐31G(d,p) thermal corrections, lead to a temperature‐dependent population in excellent agreement with the experimental results based on the analysis of the low temperature 13C NMR spectrum. The nice agreement with experiment is achieved using MP2 harmonic frequencies for the evaluation of vibration partition functions within the standard statistic thermodynamics formalism. Theoretical temperature‐dependent infrared (IR) and 13C NMR spectra were simulated and compared with experimental data, which confirmed the ab initio conformational population reported here. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007
Modification of optimal complete active space choices for the multiconfigurational spin‐tensor electron propagator method for ionization potentials
Authors: Saha Rajiv , Ma Dongxia , Yeager Danny L.
Published: September 2006

The multiconfigurational spin tensor electron propagator (MCSTEP) method was developed as an implementation of electron propagator/single particle Green's function methods. MCSTEP was specifically designed for open‐shell and highly correlated (nondynamically correlated) initial states. Ionization or electron attachment is always from a state of pure spin symmetry to a state of pure spin symmetry even if the initial state is open shell. MCSTEP can be used as well for molecules with initial states that can be accurately described by a single determinant‐based theory. The initial state that is used in MCSTEP is typically a small complete active space (CAS) multiconfigurational self‐consistent field (MCSCF) state. We previously examined different small CAS choices for MCSTEP initial states and have developed a generally workable scheme. This article further examines some different ways to choose the CAS for MCSTEP. With several logical CAS choices, we have calculated the low‐lying vertical MCSTEP ionization potentials (IPs) of C2, N2, linear H2O, O2, CH2, and NH2, comparing them with large multireference configuration interaction (MRCI) calculations. We conclude that generally a small modification and extension of our previous schemes for choosing the MCSTEP CAS gives IPs that most effectively mimics the results of large scale MRCI IPs in general. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007