bluuebunny/crossref_metadata_2025 huggingface dataset:
Osteosarcoma originates from mesenchymal stem cells in consequence of aneuploidization and genomic loss of Cdkn2
Authors: Mohseny Alexander B , Szuhai Karoly , Romeo Salvatore , Buddingh Emilie P , Briaire‐de Bruijn Inge , de Jong Daniëlle , van Pel Melissa , Cleton‐Jansen Anne‐Marie , Hogendoorn Pancras CW
Published: July 2009

High‐grade osteosarcoma is characterized by extensive genetic instability, thereby hampering the identification of causative gene mutations and understanding of the underlying pathological processes. It lacks a benign precursor lesion and reports on associations with hereditary predisposition or germline mutations are uncommon, despite the early age of onset. Here we demonstrate a novel comprehensive approach for the study of premalignant stages of osteosarcoma development in a murine mesenchymal stem cell (MSC) system that formed osteosarcomas upon grafting. By parallel functional and phenotypic analysis of normal MSCs, transformed MSCs and derived osteosarcoma cells, we provide substantial evidence for a MSC origin of osteosarcoma. In a stepwise approach, using COBRA–FISH karyotyping and array CGH in different passages of MSCs, we identified aneuploidization, translocations and homozygous loss of the cdkn2 region as the key mediators of MSC malignant transformation. We then identified CDKN2A/p16 protein expression in 88 osteosarcoma patients as a sensitive prognostic marker, thereby bridging the murine MSCs model to human osteosarcoma. Moreover, occasional reports in patients mention osteosarcoma formation following bone marrow transplantation for an unrelated malignancy. Our findings suggest a possible hazard for the clinical use of MSCs; however, they also offer new opportunities to study early genetic events in osteosarcoma genesis and, more importantly, to modulate these events and record the effect on tumour progression. This could be instrumental for the identification of novel therapeutic strategies, since the success of the current therapies has reached a plateau phase. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Post‐transplant EBV‐related lymphoproliferative disorder complicating umbilical cord blood transplantation in patients of adrenoleukodystrophy
Authors: Cheng Frankie Wai Tsoi , Lee Vincent , To Ka Fai , Chan K.C. Allen , Shing Ming Kong , Li Chi Kong
Published: July 2009

EBV‐associated post‐transplant lymphoproliferative disorder (PTLD) is a well‐recognized complication following solid organ transplantation and hematopoietic stem cell transplantation (HSCT) using bone marrow or peripheral blood as stem cell sources, but rarely reported in umbilical cord blood transplantation (UCBT). We report two cases in unrelated UCBT setting and added the following new information to the literature: (i) EBV‐related PTLD can be presented late in recipients of unrelated UCBT; (ii) in contrast to reported literatures that PTLD is a serious complication with unfavorable outcome, especially in monomorphic form, our cases showed that the clinical course may be relatively benign if treatment is initiated promptly. Pediatr Blood Cancer 2009; 53:1329–1331. © 2009 Wiley‐Liss, Inc.
Self‐assembly of π‐conjugated bis(terpyridine) ligands with zinc(II) ions: New metallosupramolecular materials for optoelectronic applications
Authors: Winter Andreas , Friebe Christian , Chiper Manuela , Hager Martin D. , Schubert Ulrich S.
Published: July 2009

A series of main‐chain metallopolymers (P1–P10) was prepared by the self‐assembly of rigid‐linear π‐conjugated bis(terpyridine) monomers (1–10) with ZnIIions and was fully characterized. The polymerization was additionally confirmed by UV/vis titration experiments. A strong increase in viscosities (around 1.6 times) relative to those of the monomer solutions was found. The thermal stability ofP1–P10compared with that of1–10was enhanced as a result of the metallopolymerization. The electro‐optical properties of the materials were investigated in detail. Tuning of the electrochemical and photophysical properties was enabled; thus, bright purple to green photoluminescent (PL) emission (PL quantum yields of 0.12–0.81) forP1–P10was observed in solution with the emission color strongly depending on the nature of the π‐conjugated bis(terpyridine) system. Thin homogeneous films ofP6were prepared by solution processing, that is, spin‐coating and inkjet‐printing, and exhibited intense yellow PL emission in the solid state. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 4083–4098, 2009
Morphological transitions in aggregates of thermosensitive poly(ethylene oxide)‐b‐poly(N‐isopropylacrylamide) block copolymers prepared via RAFT polymerization
Authors: Zhao Junpeng , Zhang Guangzhao , Pispas Stergios
Published: July 2009

Double hydrophilic poly(ethylene oxide)‐b‐poly(N‐isopropylacrylamide) (PEO‐b‐PNIPAM) block copolymers were synthesized via reversible addition‐fragmentation chain transfer (RAFT) polymerization, using a PEO‐based chain transfer agent (PEO‐CTA). The molecular structures of the copolymers were designed to be asymmetric with a short PEO block and long PNIPAM blocks. Temperature‐induced aggregation behavior of the block copolymers in dilute aqueous solutions was systematically investigated by a combination of static and dynamic light scattering. The effects of copolymer composition, concentration (Cp), and heating rate on the size, aggregation number, and morphology of the aggregates formed at temperatures above the LCST were studied. In slow heating processes, the aggregates formed by the copolymer having the longest PNIPAM block, were found to have the same morphology (spherical “crew‐cut” micelles) within the full range of Cp. Nevertheless, for the copolymer having the shortest PNIPAM block, the morphology of the aggregates showed a great dependence on Cp. Elongation of the aggregates from spherical to ellipsoidal or even cylindrical was observed. Moreover, vesicles were observed at the highest Cp investigated. Fast heating leads to different characteristics of the aggregates, including lower sizes and aggregation numbers, higher densities, and different morphologies. Thermodynamic and kinetic mechanisms were proposed to interpret these observations, including the competition between PNIPAM intrachain collapse and interchain aggregation. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 4099–4110, 2009
Barrier property enhancement of polyamide 6 by blending with a polyhydroxyamino‐ether resin
Authors: Eceolaza Sorkunde , Iriarte Marian , Uriarte Cristina , Etxeberria Agustin
Published: July 2009

In this work, the transport properties of the system formed by polyamide 6 (PA6) and polyhydroxyamino‐ether resin (PHAE) have been studied after characterizing the miscibility behavior. A single glass transition has been observed using differential scanning calorimetry that usually means total miscibility, but measurements by solid‐state cross‐polarization magic angle spinning NMR have shown that this system is only partially miscible, in good agreement with phase behavior reported before. Both carbon dioxide and water vapor transport properties of PA6/PHAE blends have been measured. For both penetrants, permeability coefficient shows an interesting negative deviation from the additive value, even the barrier character to carbon dioxide of pure PHAE is maintained up to 60 % in PA6 composition. Besides, PHAE reduces the plasticization effect of water in PA6. These improvements are very interesting for the PA 6 due to its wide use in packaging applications. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 1625–1634, 2009
Posttraumatic stress disorder symptoms in cancer: psychometric analysis of the Spanish Posttraumatic Stress Disorder Checklist‐Civilian version
Authors: Costa‐Requena Gema , Gil Francisco
Published: July 2009

Objective: The PTSD Checklist‐Civilian version (PCL‐C) was used as a screening tool to assess the presence of PTSD symptoms. The aim of this study was to explore the factorial structure of the Spanish version of the PCL‐C and calculate the correlation of PTSD symptoms with distress and health‐related quality of life.

Method: The sample included 494 cancer outpatients. In order to validate the PCL‐C, a principal component analysis was applied. The association between variable was measured by Pearson correlation.

Results: Findings evidenced three symptoms clusters on the PCL‐C version, defined as Hyperarousal/Re‐experiencing, Numbing and Avoidance. About 10% of the total sample met clinical PTSD symptoms. In addition, PTSD symptoms were related negatively to health‐related quality of life and positively related with distress.

Conclusion: The conceptualization of PTSD symptoms for cancer patients is supported by the specific symptom clusters identified on PCL‐C. Copyright © 2009 John Wiley & Sons, Ltd.
Profiling the potential biomarkers for cell differentiation of pancreatic cancer using iTRAQ and 2‐D LC‐MS/MS
Authors: Zhang Haijing , Lv Liyan , Liu Hui , Cui Lei , Chen Guoqiang , Bi Peixuan , Li Zhili
Published: July 2009

Pancreatic cancer is a highly lethal disease that is difficult to diagnose at early stage and even more difficult to cure. SW1990 and PANC‐1 represent the two cancer cell lines, which are both derived from pancreatic duct, but at different cell differentiation stages. In this study, we applied the iTRAQ‐labeling technology and 2‐D strong cation exchange/reversed phase liquid chromatography – LC‐MS/MS) to profile the secreted proteins of SW1990 and PANC‐1 cells in a conditioned cell culture medium. A total of 401 proteins were identified by MS/MS and protein database searching, the percentages of these proteins predicted in the categories of plasma membrane, intracellular and secreted proteins were 29.2, 32.7 and 38.2%, respectively. Fifty six proteins were identified with unknown functions and 19 proteins were quantified with significant level changes between the two cancer cell lines under the specific cell condition with 12 proteins being up‐regulated (>1.3‐fold change) in PANC‐1 (e.g. FLJ31222 protein, 97 kDa protein, type IV collagenase precursor, 38 kDa protein and centaurin) and seven proteins being up‐regulated in SW1990 (e.g. fibroblast growth factor receptor substrate 2, putative p150, hypothetical protein LOC 654463 and LOC 55701). The proteins with significant level changes may provide a baseline to investigate mechanisms underlying the differentiation of two cell lines and can be further screened for better protein biomarkers in pancreatic cancer.
Activity‐based mass spectrometric characterization of proteases and inhibitors in human saliva
Authors: Sun Xiuli , Salih Erdjan , Oppenheim Frank G. , Helmerhorst Eva J.
Published: July 2009

Proteases present in oral fluid effectively modulate the structure and function of some salivary proteins and have been implicated in tissue destruction in oral disease. To identify the proteases operating in the oral environment, proteins in pooled whole saliva supernatant were separated by anion‐exchange chromatography and individual fractions were analyzed for proteolytic activity by zymography using salivary histatins as the enzyme substrates. Protein bands displaying proteolytic activity were particularly prominent in the 50–75 kDa region. Individual bands were excised, in‐gel trypsinized and subjected to LC/ESI‐MS/MS. The data obtained were searched against human, oral microbial and protease databases. A total of 13 proteases were identified all of which were of mammalian origin. Proteases detected in multiple fractions with cleavage specificities toward arginine and lysine residues, were lactotransferrin, kallikrein‐1, and human airway trypsin‐like protease. Unexpectedly, ten protease inhibitors were co‐identified suggesting they were associated with the proteases in the same fractions. The inhibitors found most frequently were alpha‐2‐macroglobulin‐like protein 1, alpha‐1‐antitrypsin, and leukocyte elastase inhibitor. Regulation of oral fluid proteolysis is highly important given that an inbalance in such activities has been correlated to a variety of pathological conditions including oral cancer.
Analyses on hydrophobicity and attractiveness of all‐atom distance‐dependent potentials
Authors: Shirota Matsuyuki , Ishida Takashi , Kinoshita Kengo
Published: July 2009

Accurate model evaluation is a crucial step in protein structure prediction. For this purpose, statistical potentials, which evaluate a model structure based on the observed atomic distance frequencies in comparison with those in reference states, have been widely used. The reference state is a virtual state where all of the atomic interactions are turned off, and it provides a standard to measure the observed frequencies. In this study, we examined seven all‐atom distance‐dependent potentials with different reference states. As results, we observed that the variations of atom pair composition and those of distance distributions in the reference states produced systematic changes in the hydrophobic and attractive characteristics of the potentials. The performance evaluations with the CASP7 structures indicated that the preference of hydrophobic interactions improved the correlation between the energy and the GDT‐TS score, but decreased the Z‐score of the native structure. The attractiveness of potential improved both the correlation and Z‐score for template‐based modeling targets, but the benefit was smaller in free modeling targets. These results indicated that the performances of the potentials were more strongly influenced by their characteristics than by the accuracy of the definitions of the reference states.
Testing and improving the effectiveness of trap crops for management of the diamondback moth Plutella xylostella (L.): a laboratory‐based study
Authors: George David R , Collier Rosemary , Port Gordon
Published: July 2009

BACKGROUND: The aim of this study was to assess white mustard (Sinapis alba L.) as a trap crop for diamondback moth [Plutella xylostella (L.)] on cauliflower [Brassica oleracea (L.) var. Lateman]. Moth behaviour on these plants and the importance of plant age and size in maintaining pest preference for trap crop plants were also investigated.

RESULTS: Three times as many eggs were laid on cauliflower plants that were unprotected than on plants protected by a trap crop of white mustard. Moths remained longer on the mustard plants as a result of a doubling in the mean duration of information‐providing behaviours. Plant age had little effect on P. xylostella host preference. When plant age was constant, percentage oviposition on mustard was higher when these were larger (93%) than copresented cauliflower plants, compared with when they were smaller (68%).

CONCLUSION: Trap cropping with white mustard may reduce the incidence of P. xylostella in cauliflower crops. The pest management benefits of trap crops may be maximised by using trap crop plants that are larger than the main crop plants, although relatively smaller trap crop plants may still be preferred as hosts for P. xylostella per se. Copyright © 2009 Society of Chemical Industry
Treatment options for the management of parkinsonism
Authors: Metta Vinod , Davidson Colette , Iqbal Nausheen
Published: July 2009

Parkinson's disease is a disabling condition usually of later life for which there a variety of treatments. Our Drug review describes the symptoms and the properties of the available drugs, followed by a review of the prescription data and sources of further information. Copyright © 2009 Wiley Interface Ltd
Antimicrobial peptide interactions with silica bead supported bilayers and E. coli: buforin II, magainin II, and arenicin
Authors: Davis Ryan W. , Arango Dulce C. , Jones Howland D. T. , Van Benthem Mark H. , Haaland David M. , Brozik Susan M. , Sinclair Michael B.
Published: July 2009

Using the unique quantitative capabilities of hyperspectral confocal microscopy combined with multivariate curve resolution, a comparative approach was employed to gain a deeper understanding of the different types of interactions of antimicrobial peptides (AMPs) with biological membranes and cellular compartments. This approach allowed direct comparison of the dynamics and local effects of buforin II, magainin II, and arenicin with nanoporous silica bead supported bilayers and living E. coli. Correlating between experiments and comparing these responses have yielded several important discoveries for pursuing the underlying biophysics of bacteriocidal specificity and the connection between structure and function in various cellular environments. First, a novel fluorescence method for direct comparison of a model and living system is demonstrated by utilizing the membrane partitioning and environmental sensitivity of propidium iodide. Second, measurements are presented comparing the temporal dynamics and local equilibrium concentrations of the different antimicrobial agents in the membrane and internal matrix of the described systems. Finally, we discuss how the data lead to a deeper understanding of the roles of membrane penetration and permeabilization in the action of these AMPs. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.
Phonon spectroscopy of CdSe1–xTex nanocrystals grown in a borosilicate glass
Authors: Azhniuk Yu. M. , Hutych Yu. I. , Lopushansky V. V. , Prots L. A. , Gomonnai A. V. , Zahn D. R. T.
Published: July 2009

Phonon spectra of CdSe1–x Tex nanocrystals grown in a borosilicate glass matrix, are studied by Raman spectroscopy. The experimental data are compared to those obtained by other authors for bulk and nanoscale CdSe1–x Tex. With the account of the factors specific for glass‐embedded nanocrystals, Raman spectroscopy is shown to be a reliable and non‐destructive method to evaluate the ternary nanocrystal composition. Raman measurements performed at different excitation wavelengths enabled the compositional dispersion of the nanocrystals to be estimated. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Quantitative method of the point defect concentration determination in Zn‐ and Cd‐doped HgTe using the far‐infrared spectroscopy
Authors: Cebulski J. , Sheregii E. M. , Polit J. , Marcelli A. , Piccinini M. , Kisiel A. , Kucherenko I. V. , Triboulet R.
Published: July 2009

Our research is motivated in the first line by the necessity to have the total control of the vacancies which appear during the growth of mercury telluride crystals. As it is known, this material is very important for the IR devices. We present a non‐destructive method for quantitative determining the vacancy concentration in the lattice of Hg‐based semiconductor alloys with tetrahedral structure. The method is based on the identification of additional vibrational modes (AVM) induced by lattice deformations in the far infrared (FIR) reflectivity spectrum. Although the method is restricted by sensitivity limitations, recent FIR experimental data carried out on HgZnTe and HgCdTe samples containing Hg‐vacancies confirmed the presence of AVMs induced by Hg‐vacancies in as‐grown crystals. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Light polarized resonant Raman spectra from individual single‐ and double‐wall carbon nanotubes
Authors: Judek J. , Brunel D. , Mélin T. , Marczak M. , Zdrojek M. , Gebicki W. , Adamowicz L.
Published: July 2009

Measured light polarization dependent resonant Raman spectra from spatially isolated semiconducting single‐ and double‐wall carbon nanotubes are reported. Most of the observed modes intensities exhibit two or fourfold symmetry, for VV and VH configuration, respectively. Weak quantitative changes in the G bands have been observed suggesting different subbands transitions Evμ→Ecμ contribution. Model explaining both the angular variation and week quantitative changes is presented. Selected carbon nanotubes electronic and optical properties are studied using the ab initio calculations in order to complete the outlook. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Raman scattering on semiconductor microtubes
Authors: Milekhin Alexander , Mutilin Sergei , Yukecheva Julia , Putyato Michael , Vorob'ev Alexander , Prinz Victor , Kolchuzhin Vladimir , Mehner Jan , Zahn Dietrich R. T.
Published: July 2009

A micro‐Raman study of optical phonons in GaAs/InGaAs and InGaAs/InAs bilayer microtubes is presented. From the analysis of optical phonon frequencies the built‐in mechanical strain in the microtubes was estimated and compared with theoretical predictions. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Point defect phonons in intermetallics: NiAl3 by atomic‐scale simulation
Authors: Tingaud David , Besson Rémy
Published: July 2009

Investigating the influence of phonons on the point defect properties of D011 NiAl3 by means of an embedded‐atom potential, the present work demonstrates the importance of this factor, responsible for a large enhancement of the amounts of Al intrinsic and Ni interstitial defects, hence a complete change in the expected point defect structure of the compound, with possible consequences on matter diffusion. Moreover, new eigenfrequencies, above the DOS of the perfect crystal, are obtained around isolated Al interstitials and antisites, confirming the role of extra Al‐Al bonds in the rise of upper frequencies, a feature already noted in Ni3Al. However, such frequencies are also surprisingly detected in Ni‐rich alloys containing interstitial Ni, which suggests a Ni‐induced stiff coupling of Al atoms. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Synchrotron radiation – a brilliant source for solid‐state research in the infrared energy domain
Authors: Marcelli Augusto , Guidi Mariangela Cestelli , Piccinini Massimo , Innocenzi Plinio , Malfatti Luca , Xu Wei
Published: July 2009

IR spectroscopy probes the rotations and the vibrations of molecules, the low‐energy excitations of solids and many other low‐energy phenomena occurring in condensed matter physics, chemistry, biophysics and materials science. Here we will present some examples of experiments that can experience a great advantage by IR synchrotron radiation sources in particular in the mid‐ and far‐IR domain. FTIR spectroscopy and reflectivity measurements are non‐destructive methods that can be applied to metallic, semiconductor or insulator systems returning accurate information on vibrtional and phonon spectra as a function of external parameters such as temperature or pressure. Far‐IR spectroscopy with synchrotron radiation may be indeed used to investigate with a DAC cell pressure‐driven insulator‐to‐metal transitions, one of the most intriguing phenomena exhibited by condensed matter. Another unique applications of IR SR is time‐resolved IR spectroscopy and imaging in materials science and in biology. However, also combined time‐resolved analysis (FTIR and SAXS) using two different radiations exciting the same system in a concurrent way is a powerful technique fundamental to understand complex phenomena.

In particular, we will show how the combination of SAXS and mid‐IR spectroscopy correlates the solvent and the water evaporation kinetics explaining the structural organization of self‐assembly mesostructured films. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Carotenoids with anti‐Helicobacter pylori activity from Golden delicious apple
Authors: Molnár Péter , Deli József , Tanaka Toru , Kann Yoshiyuki , Tani Satoru , Gyémánt Nóra , Molnár Joseph , Kawase Masami
Published: July 2009

Previously it was reported that hypophasic carotenoids of Golden delicious apple peel showed potent anti‐H. pylori activity (MIC50 = 36 µg/mL), comparable to metronidazole (MIC50 = 45 µg/mL). To further investigate the involved active carotenoids of the apple peel extracts, seven carotenoids were isolated for the current study: (all‐E)‐luteoxanthin, (all‐E)‐neoxanthin, (9′Z)‐neoxanthin, (all‐E)‐antheraxanthin, (all‐E)‐violaxanthin, (9Z)‐violaxanthin and (all‐E)‐lutein. The MIC50 values of (all‐E)‐luteoxanthin, (all‐E)‐neoxanthin and (9′Z)‐neoxanthin were 7.9, 11 and 27 µg/mL, respectively. Other carotenoids and β,β‐carotene did not exhibit potent anti‐H. pylori activity (MIC50 > 100 µg/mL). An examination of structure and function suggested that active carotenoids contained a monofuranoid ring or an allenic bond in addition to an epoxy group and an additional two or three hydroxyl substituents on the side group. Copyright © 2009 John Wiley & Sons, Ltd.
Ensemble propagation and continuous matrix factorization algorithms
Authors: Bergemann Kay , Gottwald Georg , Reich Sebastian
Published: July 2009

We consider the problem of propagating an ensemble of solutions and its characterization in terms of its mean and covariance matrix. We propose differential equations that lead to a continuous matrix factorization of the ensemble into a generalized singular value decomposition (SVD). The continuous factorization is applied to ensemble propagation under periodic rescaling (ensemble breeding) and under periodic Kalman analysis steps (ensemble Kalman filter). We also use the continuous matrix factorization to perform a re‐orthogonalization of the ensemble after each time‐step and apply the resulting modified ensemble propagation algorithm to the ensemble Kalman filter. Results from the Lorenz‐96 model indicate that the re‐orthogonalization of the ensembles leads to improved filter performance. Copyright © 2009 Royal Meteorological Society
CUSUM charts for detecting special causes in integrated process control
Authors: Reynolds Marion R. , Park Changsoon
Published: July 2009

This paper investigates control charts for detecting special causes in an ARIMA(0, 1, 1) process that is being adjusted automatically after each observation using a minimum mean‐squared error adjustment policy. It is assumed that the adjustment mechanism is designed to compensate for the inherent variation due to the ARIMA(0, 1, 1) process, but it is desirable to detect and eliminate special causes that occur occasionally and produce additional process variation. It is assumed that these special causes can change the process mean, the process variance, the moving average parameter, or the effect of the adjustment mechanism. Expressions are derived for the process deviation from target for all of these process parameter changes. Numerical results are presented for sustained shifts, transient shifts, and sustained drifts in the process parameters. The objective is to find control charts or combinations of control charts that will be effective for detecting special causes that result in any of these types of parameter changes in any or all of the parameters. CUSUM charts designed for detecting specific parameter changes are considered. It is shown that combinations of CUSUM charts that include a CUSUM chart designed to detect mean shifts and a CUSUM chart of squared deviations from target give good overall performance in detecting a wide range of process changes. Copyright © 2009 John Wiley & Sons, Ltd.
Analyzing unreplicated 2k factorial designs by examining their projections into k‐1 factors
Authors: Angelopoulos P. , Evangelaras H. , Koukouvinos C.
Published: July 2009

Unreplicated factorial designs are widely used as experimental designs because of the economy they offer in run size. However, they are difficult to analyze because there are no degrees of freedom left to estimate the experimental error. Many methods have been proposed for the analysis of such designs with Lenth's (Technometrics 1989; 31:469–473) and Dong's (Statist. Sinica 1993; 3:209–217) being the most popular. In this paper we take advantage of the projective property of factorial designs and we propose a simple yet effective method for analyzing unreplicated factorial designs. The results are compared through a simulation study with Lenth's and Dong's methods. Copyright © 2009 John Wiley & Sons, Ltd.
When are summary ROC curves appropriate for diagnostic meta‐analyses?
Authors: Chappell F. M. , Raab G. M. , Wardlaw J. M.
Published: July 2009

Diagnostic tests are increasingly evaluated with systematic reviews and this has lead to the recent developments of statistical methods to analyse such data. The most commonly used method is the summary receiver operating characteristic (SROC) curve, which can be fitted with a non‐linear bivariate random‐effects model. This paper focuses on the practical problems of interpreting and presenting data from such analyses. First, many meta‐analyses may be underpowered to obtain reliable estimates of the SROC parameters. Second, the SROC model may be inappropriate. In these situations, a summary with two univariate meta‐analyses of the true and false positive rates (TPRs and FPRs) may be more appropriate. We characterize the type of problems that can occur in fitting these models and present an algorithm to guide the analyst of such studies, with illustrations from analyses of published data. A set of R functions, freely available to perform these analyses, can be downloaded from (www.diagmeta.info). Copyright © 2009 John Wiley & Sons, Ltd.
Contactless Electrofunctionalization of a Single Pore
Authors: Bouchet Aurélie , Descamps Emeline , Mailley Pascal , Livache Thierry , Chatelain François , Haguet Vincent
Published: July 2009

Customized pores are smart components that find challenging applications in a variety of fields including purification membranes and biosensing systems. The incorporation of recognition probes within pores is therefore a challenge, due to the technical difficulty of delimiting the area functionalized and obtaining the localized, specific chemical modification of pore walls. An innovative approach, named contactless electrofunctionalization (CLEF), is presented to overcome this problem. CLEF allows easy, one‐step modification of the inner surface of a pore etched in a dielectric membrane. The pore wall is coated under the influence of an electric field created by the application of a voltage between two electrodes, located near but not in contact with the pore openings. This specific localization of the deposited material within the pore is extremely rapid. Coatings were reliably and reproducibly obtained using polypyrrole co‐polymers bearing oligonucleotides, demonstrating that this technology has a promising future in the design of biosensors. Moreover, the versatility of this process allows the deposition of various electroactive entities such as iridium oxide and therefore indicates a strong potential for diverse applications involving porous materials.
Neural Stem Cell Transplantation Benefits a Monogenic Neurometabolic Disorder During the Symptomatic Phase of Disease
Authors: Jeyakumar Mylvaganam , Lee Jean-Pyo , Sibson Nicola R. , Lowe John P. , Stuckey Daniel J. , Tester Katie , Fu Gerald , Newlin Robin , Smith David A. , Snyder Evan Y. , Platt Frances M.
Published: July 2009

Although we and others have demonstrated that neural stem cells (NSCs) may impact such neurogenetic conditions as lysosomal storage diseases when transplanted at birth, it has remained unclear whether such interventions can impact well-established mid-stage disease, a situation often encountered clinically. Here we report that when NSCs were injected intracranially into the brain of adult symptomatic Sandhoff (Hexb−/−) mice, cells migrated far from the injection site and integrated into the host cytoarchitecture, restoring β-hexosaminidase enzyme activity and promoting neuropathologic and behavioral improvement. Mouse lifespan increased, neurological function improved, and disease progression was slowed. These clinical benefits correlated with neuropathological correction at the cellular and molecular levels, reflecting the multiple potential beneficial actions of stem cells, including enzyme cross-correction, cell replacement, tropic support, and direct anti-inflammatory action. Pathotropism (i.e., migration and homing of NSCs to pathological sites) could be imaged in real time by magnetic resonance imaging. Differentially expressed chemokines might play a role in directing the migration of transplanted stem cells to sites of pathology. Significantly, the therapeutic impact of NSCs implanted in even a single location was surprisingly widespread due to both cell migration and enzyme diffusion. Because many of the beneficial actions of NSCs observed in newborn brains were recapitulated in adult brains to the benefit of Sandhoff recipients, NSC-based interventions may also be useful in symptomatic subjects with established disease.

Disclosure of potential conflicts of interest is found at the end of this article.
Acetylation of Sox2 Induces its Nuclear Export in Embryonic Stem Cells
Authors: Baltus Gretchen A. , Kowalski Michael P. , Zhai Huili , Tutter Antonin V. , Quinn Douglas , Wall Daniel , Kadam Shilpa
Published: July 2009

Embryonic stem (ES) cells require a coordinated network of transcription factors to maintain pluripotency or trigger lineage specific differentiation. Central to these processes are the proteins Oct4, Nanog, and Sox2. Although the transcriptional targets of these factors have been extensively studied, very little is known about how the proteins themselves are regulated, especially at the post-translational level. Post-translational modifications are well documented to have broad effects on protein stability, activity, and cellular distribution. Here, we identify a key lysine residue in the nuclear export signal of Sox2 that is acetylated, and demonstrate that blocking acetylation at this site retains Sox2 in the nucleus and sustains expression of its target genes under hyperacetylation or differentiation conditions. Mimicking acetylation at this site promotes association of Sox2 with the nuclear export machinery. In addition, increased cellular acetylation leads to reduction in Sox2 levels by ubiquitination and proteasomal degradation, thus abrogating its ability to drive transcription of its target genes. Acetylation-mediated nuclear export may be a commonly used regulatory mechanism for many Sox family members, as this lysine is conserved across species and in orthologous proteins.

Disclosure of potential conflicts of interest is found at the end of this article.
Cardiac c-kit+AT2+ Cell Population is Increased in Response to Ischemic Injury and Supports Cardiomyocyte Performance
Authors: Altarche-Xifró Wassim , Curato Caterina , Kaschina Elena , Grzesiak Aleksandra , Slavic Svetlana , Dong Jun , Kappert Kai , Steckelings Muscha , Imboden Hans , Unger Thomas , Li Jun
Published: July 2009

The expression pattern of angiotensin AT2 receptors with predominance during fetal life and upregulation under pathological conditions during tissue injury/repair process suggests that AT2 receptors may exert an important action in injury/repair adaptive mechanisms. Less is known about AT2 receptors in acute ischemia-induced cardiac injury. We aimed here to elucidate the role of AT2 receptors after acute myocardial infarction. Double immunofluorescence staining showed that cardiac AT2 receptors were mainly detected in clusters of small c-kit+ cells accumulating in peri-infarct zone and c-kit+AT2+ cells increased in response to acute cardiac injury. Further, we isolated cardiac c-kit+AT2+ cell population by modified magnetic activated cell sorting and fluorescence activated cell sorting. These cardiac c-kit+AT2+ cells, represented ∼0.19% of total cardiac cells in infarcted heart, were characterized by upregulated transcription factors implicated in cardiogenic differentiation (Gata-4, Notch-2, Nkx-2.5) and genes required for self-renewal (Tbx-3, c-Myc, Akt). When adult cardiomyocytes and cardiac c-kit+AT2+ cells isolated from infarcted rat hearts were cocultured, AT2 receptor stimulation in vitro inhibited apoptosis of these cocultured cardiomyocytes. Moreover, in vivo AT2 receptor stimulation led to an increased c-kit+AT2+ cell population in the infarcted myocardium and reduced apoptosis of cardiomyocytes in rats with acute myocardial infarction. These data suggest that cardiac c-kit+AT2+ cell population exists and increases after acute ischemic injury. AT2 receptor activation supports performance of cardiomyocytes, thus contributing to cardioprotection via cardiac c-kit+AT2+ cell population.
The dopaminergic stabilizer ASP2314/ACR16 selectively interacts with D2High receptors
Authors: Seeman Philip , Tokita Kenichi , Matsumoto Mitsuyuki , Matsuo Ayako , Sasamata Masao , Miyata Keiji
Published: July 2009

Dopaminergic stabilizers are recognized as compounds that can either enhance or antagonize dopamine (DA)‐dependent behaviors depending on the prevailing dopaminergic tone. The dopaminergic stabilizer ASP2314 is being tested clinically and has been reported to have antipsychotic effects in a clinical trial as an add on medication. To elucidate the mechanisms of action of this dopaminergic stabilizer, its potency on the functional dopamine D2High receptors was examined. In competition with D2 receptors selectively labeled by [3H]domperidone, ASP2314 had a dissociation constant, KiHigh, of 1.62 μM for D2High in human cloned D2Long receptors and 0.83 μM for rat homogenized striata. Using the D2 agonist ligand [3H](+)‐4‐propyl‐3,4,4a,5,6,10b‐hexahydro‐2H‐naphtho[1,2‐b][1,4]oxazin‐9‐ol ((+)PHNO), ASP2314 had a high‐affinity Ki of 32 nM for D2High for rat homogenized striata. ASP2314 stimulated the incorporation of [35S]GTP‐γ‐S into rat striata by 50% at 43 nM, and into the cloned D2Long membranes by 50% at 3.2 μM (compared to 100% stimulation by 10 μM dopamine). With similar concentrations of ASP2314 inhibiting the binding of ligands at D2High and stimulating [35S]GTP‐γ‐S incorporation, the data indicate that the dopaminergic stabilizing action of ASP2314 may be related to the selectivity for the D2high state of the D2 receptor. Synapse 63:930–934, 2009. © 2009 Wiley‐Liss, Inc.
Role of GABA transporter 3 in GABAergic synaptic transmission at striatal output neurons
Authors: Kirmse Knut , Kirischuk Sergei , Grantyn Rosemarie
Published: July 2009

Striatal GABAergic signaling has been shown to be essential for basal ganglia output and proper motor performance. In the mouse neostriatum GABA transporter 1 (GAT‐1) was previously found to assist in the clearance of GABA from the extracellular space and influence both phasic and tonic GABAergic inhibition of medium‐sized striatal output neurons (SONs). It currently remains unknown whether GAT subtypes other than GAT‐1 participate in the modulation of GABAergic transmission in this brain structure. In this study, we aimed at assessing the role of GAT‐3 in the mouse neostriatum. To this end, we recorded GABAergic inhibitory postsynaptic currents (IPSCs) from SONs in brain slices at different developmental stages (postnatal days (P) 7‐9, 12‐14, and 28‐34) using the whole‐cell patch‐clamp technique. When applied under control conditions, SNAP‐5114 (40 μM), a specific GAT‐3 blocker, did not affect miniature or evoked IPSCs (m/eIPSCs) and produced no significant effect on tonic GABAA receptor‐mediated conductances in SONs. However, in the presence of NO‐711 (10 μM), a specific GAT‐1 blocker, SNAP‐5114 reduced mIPSC frequencies without affecting mIPSC amplitudes or kinetics. In addition, SNAP‐5114 reduced the mean amplitude of eIPSCs and increased the paired‐pulse ratio. These effects were entirely abolished by CGP55845 (1 μM), a specific GABAB receptor blocker, indicating that they were mediated by presynaptic GABAB receptors. Similar results were obtained from all age groups. We conclude that GAT‐3 is functionally expressed in the mouse neostriatum. Whereas an acute block of GAT‐3 under resting conditions is fully compensated for by GAT‐1, GAT‐3 might provide an additional uptake capacity when neuronal activity and GABA release are increased. Synapse 63:921–929, 2009. © 2009 Wiley‐Liss, Inc.
Glutamate agonist LY404,039 for treating schizophrenia has affinity for the dopamine D2High receptor
Authors: Seeman Philip , Guan Hong‐Chang
Published: July 2009

The glutamate agonist LY404,039 has been used to treat schizophrenia. Because all currently used antipsychotics act on dopamine receptors, it was decided to examine whether this glutamate agonist also had an affinity for dopamine D2 receptors in vitro. The present data show that LY404,039 inhibited the binding of [3H]domperidone and [3H](+)PHNO by 15.5 ± 1.5% to the high‐affinity state, D2High, of cloned dopamine D2Long receptors and rat striatal tissue with dissociation constants of between 8.2 and 12.6 nM. This high‐affinity component of LY404,039 on the binding of [3H]domperidone was inhibited by the presence of guanine nucleotide, indicating an agonist action of the drug at D2High. LY404,039 also stimulated the incorporation of [35S]GTP‐γ‐S into D2Long receptors (EC50% = 80 ± 15 nM) over the same range of concentrations as occurred for the inhibition of [3H]domperidone by LY404,039 at D2High (IC50%High = 50 ± 10 nM). A possible clinical antipsychotic action of LY404,039 may depend on the combined stimulation of glutamate receptors and a partial dopamine agonist action that would interfere with neurotransmission at D2High receptors. Synapse 63:935–939, 2009. © 2009 Wiley‐Liss, Inc.
C2‐Symmetric Group 4 Metal Complexes Adorned with Chiral N,O Chelates: Synthesis and Structural Characterization of Helical Hexacoordinate Metal Dichlorides Derived from 6‐Isopropyl‐3‐methyl‐2‐(4‐isopropyl‐4,5‐dihydrooxazol‐2‐yl)phenol Ligands
Authors: Lee Jong‐Dae , Kim Tae‐Jin , Han Won‐Sik , Han Su Jung , Lee Chongmok , Ko Jaejung , Kang Sang Ook
Published: July 2009

A series of group 4 metal complexes containing [6‐isopropyl‐3‐methyl‐2‐(4‐R‐4,5‐dihydrooxazol‐2‐yl)phenol] ligands, N,O‐(OzR–OPh) [OzR = oxazolyl; R = iPr (4), tBu (5); OPh = phenolate] was prepared. The reaction of the lithium salts of compounds 4 and 5 with MCl4, (M = Ti, Zr, Hf) in 2:1 ratio afforded the corresponding hexacoordinate metal complexes of the types [{N,O‐(OziPr–OPh)}2MCl2] [M = Ti (6), Zr (7), Hf (8)] and [{N,O‐(OztBu–OPh)}2MCl2] [M = Ti (9), Zr (10), Hf (11)], respectively. The molecular structures of 6, 7, and 8 were established by X‐ray structural studies. The structures showed a helical screw‐shaped molecular entity with two alternating N,O‐chelating ancillary ligands and two cis‐chlorido ligands at the metal centers. In the case of compound 6, chiral locking by two N,O‐chelating ligands at the titanium resulted in unusual air stability. The cyclic voltammogram showed electrochemically quasireversible reduction for compound 6, whereby the half‐life of the reduction state was about 3 s.
Syntheses, Characterization and X‐ray Structure of the First Silver(I) Complexes with 4‐Amino‐3‐thioxo‐3,4‐dihydro‐1,2,4‐triazin‐5(2H)‐one
Authors: Tabatabaee Masoumeh , Ghassemzadeh Mitra , Neumüller Bernhard
Published: July 2009

Reaction of thiocarbohydrazide with glyoxolic acid monohydrate led to 4‐amino‐3‐thioxo‐3,4‐dihydro‐1,2,4‐triazin‐5(2H)‐one (AHTTO, 1). Treatment of 1 with AgNO3 and PPh3 gave thecomplexes [(PPh3)2Ag2(μ‐N,S‐AHTTO)2](NO3)2 (2) and [(PPh3)2Ag(AHTTO)]NO3·MeOH (3) was obtained under different conditions. All the compounds have been characterized by elemental analyses, IR spectroscopy and X‐ray diffraction studies.
Synthesis and Characterization of Magnesium Pyroborate by Solution Combustion and Conventional Ceramic Methods: A Comparative Study
Authors: Altuntaş Öztaş Nurşen , Erdoğan Halil
Published: July 2009

Solution Combustion Synthesis (SCS) and ConventionalCeramic Process (CCP) were applied for the preparation of magnesium pyroborate (Mg2B2O5) from Mg(NO3)2·6H2O and H3BO3. Structural and morphological properties of the products were comparatively examined by XRD and FT‐IR spectroscopic measurements as well as SEM and BET techniques. The effects of synthesis conditions on the properties of products were investigated throughly by optimizing the B/Mg molar ratio and reaction duration in CCP and by optimizing the fuel (carbohydrazide) quantity in SCS. Pure Mg2B2O5 (triclinicsuanite) was obtained by thermal treatment in CCP employing a B/Mg molar ratio of 3:1. It was found that the fuel must be in close proximity to the stoichiometric requirements in order to obtain the desired product in highly crystalline form from SCS. The Mg2B2O5 samples obtained by both methods exhibited similar structural properties but different morphologies.
Synthesis and Structural Analysis of New Palladium(II) Thiosaccharinates with Triphenylphosphane or Diphosphanes
Authors: Tarulli Susana H. , Quinzani Oscar V. , Mandolesi Sandra D. , Guida Jorge A. , Echeverría Gustavo A. , Piro Oscar E. , Castellano Eduardo E.
Published: July 2009

A series of palladium(II) thiosaccharinates with triphenylphosphane (PPh3), bis(diphenylphosphanyl)methane (dppm), and bis(diphenylphosphanyl)ethane (dppe) have been prepared and characterized. From mixtures of thiosaccharin, Htsac, and palladium(II) acetylacetonate, Pd(acac)2, the palladium(II) thiosaccharinate, Pd(tsac)2 (tsac: thiosaccharinate anion) (1) was prepared. The reaction of 1 with PPh3, dppm, and dppe leads to the mononuclear species Pd(tsac)2(PPh3)2·MeCN (2), [Pd(tsac)2(dppm)] (3), Pd(tsac)2(dppm)2 (4), and [Pd(tsac)2(dppe)]·MeCN (5). Compounds 2, 4, and 5 have been prepared also by the reaction of Pd(acac)2 with the corresponding phosphane and Htsac. All the new complexes have been characterized by chemical analysis, UV/Vis, IR, and Raman spectroscopy. Some of them have been also characterized by NMR spectroscopy. The crystalline structures of complexes 3, and 5 have been studied by X‐ray diffraction techniques. Complex 3 crystallizes in the monoclinic space group P21/n with a = 16.3537(2), b = 13.3981(3), c = 35.2277(7) Å, β = 91.284(1)°, and Z = 8 molecules per unit cell, and complex 5 in P21/n with a = 10.6445(8), b = 26.412(3), c = 15.781(2) Å, β = 107.996(7)°, and Z = 4. In compounds 3 and 5, the palladium ions are in a distorted square planar environment. They are closely related, having two sulfur atoms of two thiosaccharinate anions, and two phosphorus atoms of one molecule of dppm or dppe, respectively, bonded to the PdII atom. The molecular structure of complex 3 is the first reported for a mononuclear PdII‐dppm‐thionate system.
Synthesis, Crystal Structure, and Thermal Behavior of [BiAg3Br6(PPh3)6] and [Bi3Ag6(SPh)6Cl3(PPhiPr2)3]
Authors: Sommer Heino , Eichhöfer Andreas , Fenske Dieter
Published: July 2009

The synthesis and structural characterization of two silver bismuth complexes [BiAg3Br6(PPh3)6] (1) and [Bi3Ag6(SPh)12Cl3(PPhiPr2)3] (2) is reported. Complex 1 can be obtained from the reaction of BiBr3 with AgPhCO2, PhSSiMe3, and PPh3. The reaction of bismuth(III) chloride (BiCl3) and silverbenzoate (AgPhCO2) with PhSSiMe3 in the presence of PPhiPr2 in DME leads to [Bi3Ag6(SPh)12Cl3(PPhiPr2)3] (2). The crystal structures of the compounds were determined by X‐ray analysis of single crystals, and the thermal behavior of the compounds was investigated.
CoGa2O4 Nanoparticles and Films Using a Single Molecular Source
Authors: Mathur Sanjay , Cavelius Christian , Shen Hao
Published: July 2009

Mixed‐metal tert‐butoxide, [CoGa2(OtBu)8], was employed in the chemical vapor deposition (CVD) and sol‐gel processes to obtain thin films and nanoparticles of spinel CoGa2O4 phase, respectively. The appropriate Co:Ga ratio and intact vaporization (115–120 °C / 10–2 Torr) of the molecular source produced crystalline deposits of CoGa2O4 at relatively low temperatures (~ 500 °C). A clean transformation of the heterometal precursor in spinel oxide of definite composition was supported by TG/DTA analysis that showed no weight loss above 470 °C. The SEM images of CoGa2O4 films showed homogeneous morphology and dense microstructure constituted by nanometric grains (, ~ 35 nm). Hydrolytic decomposition of the precursor produced gels that upon heat‐treatment (400–1200 °C) formed nanoscaled spinel. For comparison, CoGa2O4 was also prepared by complexing Co2+ and Ga3+ ions with glycolate ligands, significant agglomeration effect, broader size dispersion and amorphous domains were observed indicating that low‐temperature synthesis of monophasic materials following conventional chemical approaches is hampered by thermodynamic impediments. The UV/Vis spectra of CoGa2O4 particles exhibit characteristic peaks corresponding to 4A2(F) → 4T1(P) transition in the divalent cobalt cation. The magnetization data of the CoGa2O4 nanoparticles showed as expected an antiferromagentic behavior.