bluuebunny/crossref_metadata_2025 huggingface dataset:
Mosaic maternal uniparental disomy of chromosome 15 in Prader–Willi syndrome: Utility of genome‐wide SNP array
Authors: Izumi Kosuke , Santani Avni B. , Deardorff Matthew A. , Feret Holly A. , Tischler Tanya , Thiel Brian D. , Mulchandani Surabhi , Stolle Catherine A. , Spinner Nancy B. , Zackai Elaine H. , Conlin Laura K.
Published: December 2012

Prader–Willi syndrome is caused by the loss of paternal gene expression on 15q11.2–q13.2, and one of the mechanisms resulting in Prader–Willi syndrome phenotype is maternal uniparental disomy of chromosome 15. Various mechanisms including trisomy rescue, monosomy rescue, and post fertilization errors can lead to uniparental disomy, and its mechanism can be inferred from the pattern of uniparental hetero and isodisomy. Detection of a mosaic cell line provides a unique opportunity to understand the mechanism of uniparental disomy; however, mosaic uniparental disomy is a rare finding in patients with Prader–Willi syndrome. We report on two infants with Prader–Willi syndrome caused by mosaic maternal uniparental disomy 15. Patient 1 has mosaic uniparental isodisomy of the entire chromosome 15, and Patient 2 has mosaic uniparental mixed iso/heterodisomy 15. Genome‐wide single‐nucleotide polymorphism array was able to demonstrate the presence of chromosomally normal cell line in the Patient 1 and trisomic cell line in Patient 2, and provide the evidence that post‐fertilization error and trisomy rescue as a mechanism of uniparental disomy in each case, respectively. Given its ability of detecting small percent mosaicism as well as its capability of identifying the loss of heterozygosity of chromosomal regions, genome‐wide single‐nucleotide polymorphism array should be utilized as an adjunct to the standard methylation analysis in the evaluation of Prader–Willi syndrome. © 2012 Wiley Periodicals, Inc.
Synthesis, structural characterization and in vitro cytotoxic activity of novel polymeric triorganotin(IV) complexes of urocanic acid
Authors: Camacho‐Camacho Carlos , Rojas‐Oviedo Irma , Garza‐Ortiz Ariadna , Cárdenas Jorge , Toscano Rubén Alfredo , Gaviño Rubén
Published: December 2012

Two novel triorganotin carboxylate complexes of the biologically active urocanic acid have been synthesized and characterized. Elemental analysis, melting point, spectroscopic techniques – IR, 1H, 13C and 119Sn NMR – mass spectrometry and X‐ray diffraction studies have been used for structural characterization. Crystal structures of the tin(IV) derivatives show that urocanic acid acts as a bridging bidentate ligand through its imidazole nitrogen atom and its carboxylic group, producing a polymeric one‐dimensional chain. The molecular structures of the complexes, catena‐poly‐tri(n‐butyl)tin(IV) 3‐(3H‐imidazol‐4‐yl)prop‐2‐enoate (1) and catena‐poly‐triphenyltin(IV) 3‐(3H‐imidazol‐4‐yl)prop‐2‐enoate (2), present a distorted trigonal–bipyramidal configuration. This is further confirmed by 119Sn NMR in the solid state. The tin(IV) derivatives form double‐stranded ribbons via N―H…O―H bonds. Nevertheless, the compounds are essentially monomeric in solution, with a tetrahedral configuration as observed by 119Sn NMR in solution. The cytotoxic activity of the titled compounds has been tested against six human cell lines and the corresponding IC50 values are reported. Both tin(IV) compounds have a high to very high in vitro cytotoxic activity against the tumor cell lines K562, HCT‐15 and MCF‐7. Compound 1 is 86 times more active than cisplatin in the HTC‐15 cell line. Copyright © 2012 John Wiley & Sons, Ltd.
Crystallization kinetics of bacterial poly(3‐hydroxylbutyrate) copolyesters with cyanuric acid as a nucleating agent
Authors: Pan Pengju , Shan Guorong , Bao Yongzhong , Weng Zhixue
Published: December 2012

Effects of cyanuric acid (CA) on nonisothermal and isothermal crystallization, melting behavior, and spherulitic morphology of bacterial copolyesters of poly(3‐hydroxybutyrate), i.e., poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHBV) and poly(3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate) (PHBH), have been investigated. CA has excellent acceleration effectiveness on the melt crystallization of bacterial PHB, PHBV, and PHBH, better than the nucleating agents reported in the literatures, such as boron nitride, uracil, and orotic acid. PHBV and PHBH do not crystallize upon cooling from the melt at 10°C/min, while they are able to complete crystallization under the same conditions with an addition of 1% CA, with a presence of sharp crystallization exotherm at 75–95°C. Isothermal crystallization kinetics of neat and CA‐containing PHBV and PHBH were analyzed by Avrami model. Crystallization half‐times (t1/2) of PHBV and PHBH decrease dramatically with an addition of CA. The melting behavior of isothermally melt‐crystallized PHBV and PHBH is almost not influenced by CA. Spherulitic numbers of PHBV and PHBH increase and the spherulite sizes reduce with an incorporation of CA. Nucleation densities of PHBV and PHBH increase by 3–4 orders of magnitude with a presence of 1% CA. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Synthesis and evaluation of trimethylolpropane triacrylate crosslinked superabsorbent polymers for conserving water and fertilizers
Authors: Venkatachalam Dhanapal , Vediappan Vijayakumar , Kaliappa gounder Subramanian
Published: December 2012

A series of superabsorbent polymers (SAP) were synthesized by free radical thermal copolymerization of acrylic acid and N‐isopropyl acrylamide monomers using trimethylolpropane triacrylate as crosslinker. They were characterized by FT‐IR and thermal stability (TGA/DTG), and evaluated for their water and fertilizer uptake and release characteristics under different crosslinker levels, temperature, pressure, and pH. The observed maximum absorption of water by the SAP was 1130 g/g of polymer. The release was modeled which showed a non‐Fickian mechanism. The water uptake of SAP was correlated with the average molecular weight between the crosslinks and crosslink density. Analysis of the weight loss data from TG in air revealed a zero order kinetics for the initial degradation step with an activation energy (AE) of 70.8 kJ/mol. The AEs for water uptake and release for thermal degradation were also determined through Arrhenius plots. The results inferred that the synthesized SAP can be exploited for commercial agricultural applications. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Hydrodynamics Characterization of an Ellipse Gate Impeller by Experimental and Numerical Studies
Authors: Xie M.‐H. , Xia J.‐Y. , Zhou G.‐Z. , Zhang S.‐L. , Yu P.‐Q.
Published: December 2012

Hydrodynamics characteristics like flow pattern, shear rate distribution, power consumption, axial pumping capacity, mixing time, and mixing efficiency of an ellipse gate (EG) impeller were investigated by experimental and numerical methods. The numerical simulation results were validated by experimental data of power consumption and mixing time. Results indicate that the axial pumping number of the EG impeller is larger than that of any other reported large‐scale impeller under laminar regime, and that the shear rate formed by this impeller is less sensitive to Reynolds numbers. In‐depth analysis reveals the different function of each part of the EG impeller under different flow regimes. This impeller provides an almost similar mixing efficiency like the double‐helical ribbon impeller under laminar regime, but much higher mixing efficiency both under transitional and turbulent flow regimes.
Quantum‐Chemical and Electrochemical Investigation of the Electrochemical Windows of Halogenated Carborate Anions
Authors: Boeré René T. , Bolli Christoph , Finze Maik , Himmelspach Alexander , Knapp Carsten , Roemmele Tracey L.
Published: December 2012

The range of electrochemical stability of a series of weakly coordinating halogenated (Hal=F, Cl, Br, I) 1‐carba‐closo‐dodecaborate anions, [1‐R‐CB11X5Y6]− (R=H, Me; X=H, Hal, Me; Y=Hal), has been established by using quantum chemical calculations and electrochemical methods. The structures of the neutral and dianionic radicals, as well as the anions, have been optimized by using DFT calculations at the PBE0/def2‐TZVPP level. The calculated structures are in good agreement with existing experimental data and with previous calculations. Their gas‐phase ionization energies and electron affinities were calculated based on their optimized structures and were compared with experimental (cyclic and square‐wave) voltammetry data. Electrochemical oxidation was performed in MeCN at room temperature and in liquid sulfur dioxide at lower temperatures. All of the anions show a very high resistance to the onset of oxidation (2.15–2.85 V versus Fc0/+), with only a minor dependence of the oxidation potential on the different halogen substituents. In contrast, the reduction potentials in MeCN are strongly substituent dependent (−1.93 to −3.32 V versus Fc0/+). The calculated ionization energies and electron affinities correlate well with the experimental redox potentials, which provide important verification of the thermodynamic validity of the mostly irreversible redox processes that are observed for this series. The large electrochemical windows that are afforded by these anions indicate their suitability for electrochemical applications, for example, as supporting electrolytes.
New Vistas in N‐Heterocyclic Silylene (NHSi) Transition‐Metal Coordination Chemistry: Syntheses, Structures and Reactivity towards Activation of Small Molecules
Authors: Blom Burgert , Stoelzel Miriam , Driess Matthias
Published: December 2012

This account is a review on the synthesis and transition‐metal coordination chemistry of N‐heterocyclic silylenes (NHSi’s) over the last 20 years till the present time (2012). Recently, fascinating and novel synthetic methods have been developed to access transition‐metal–NHSi complexes as an emerging class of compounds with a wealth of intriguing reactivity patterns. The striking influence of coordinating NHSi’s to transition‐metal complex fragments affording different reactivities to the “free” NHSi is a connecting theme (“leitmotif”) throughout the review, and highlights the potential of these compounds which lie at the interface of contemporary main‐group and classical organometallic chemistry towards new molecular catalysts for small‐molecule activation.
Cu2O‐Mediated Room Temperature Cyanation of Aryl Boronic Acids/Esters and TMSCN
Authors: Ye Yong , Wang Yanhua , Liu Pengtang , Han Fushe
Published: December 2012

A method for the efficient and reliable synthesis of aryl nitriles via the Cu2O‐catalyed cross‐coupling of aryl boronic acids or esters and TMSCN is presented. A broad range of substrates decorated by electron‐rich and deficient, sterically very congested, and labile functionalities were tolerated. Moreover, the reaction can proceed under mild conditions at room temperature. These advantages paired with the use of cheap, readily available, and halogen‐free Cu2O as catalysts make the protocol an appealing option for aryl cyanations.
A Highly Selective Colorimetric Sensor for Cu2+ Based on Phenolic Group Biscarbonyl Hydrazone
Authors: Li Junjian , Guo Ying , Yao Hong , Lin Qi , Xie Yongqiang , Wei Taibao , Zhang Youming
Published: December 2012

A novel copper selective sensor 2 based on hydrazide and salicylaldehyde has been designed and prepared. Sensor 2 behaves a single selectivity and sensitivity in the recognition for Cu2+ over other metal ions such as Fe3+, Hg2+, Ag+, Ca2+, Zn2+, Pb2+, Cd2+, Ni2+, Co2+, Cr3+ and Mg2+ in DMSO. The distinct color change and the rapid changement of fluorescence emission provide naked‐eyes detection for Cu2+. The UV‐vis data indicate that 1:2 stoichiometry complex is formed by sensor 2 and Cu2+. The association constant Ks was 3.51×104 mol−1·L. The detection limitation of Cu2+ with the sensor 2 was 2.2×10−7 mol·L−1. The sensing of Cu2+ by this sensor was found to be reversible, with the Cu2+‐induced color being lost upon addition of EDTA.
Palladium‐Catalyzed Cyclocarbonylation of 2‐Halobenzaldehyde and Hydrazines: A Facile Synthesis of 2‐Aminoisoindolin‐1‐ones
Authors: Han Chao , Shen Yang , Lu Ping , Wang Yanguang
Published: December 2012

An efficient procedure for the synthesis of 2‐aminoisoindolin‐1‐ones via a palladium‐catalyzed three‐component reaction of 2‐halobenzaldehydes, hydrazines and carbon monoxide is reported. This cyclocarbonylation process can be performed smoothly under 1 atmospheric pressure of carbon monoxide to afford 2‐aminoisoindolin‐1‐ones in moderate to excellent yields.
Dysoxylumasins A–F: Six New Limonoids from Dysoxylum mollissimum Bl.
Authors: Xu Jinbiao , Ni Gang , Yang Shengping , Yue Jianmin
Published: December 2012

Six new mexicanolide‐type limonoids, dysoxylumasins A–F (1–6), together with eight known compounds, namely litseagermacrane, 15‐methoxyisodauc‐3‐ene‐1β,5α‐diol, isodauc‐6‐ene‐10β,14‐diol, 4‐epi‐isodauc‐6‐ene‐10β,14‐diol, 2α,3α,4β‐trihydroxypregnan‐16‐one, 1,7‐phenanthrenedimethanol, spicatin, and aurantiamide, were isolated from the leaves and twigs of Dysoxylum mollissimum Bl. Their structures were established by the analyses of spectroscopic data.
Direct Electrochemistry of Hemoglobin on Vertically Aligned Carbon Hybrid TiO2 Nanotubes and Its Highly Sensitive Biosensor Performance
Authors: Liu Meichuan , Zhao Guohua , Tang Yiting , Shi Huijie , Yang Nianjun
Published: December 2012

The present work is focused on developing a novel biomaterial platform to achieve enhanced direct electron transfer (DET) of hemoprotein and higher biosensor performance on vertically aligned carbon hybrid TiO2 nanotubes (C‐TiO2 NTs). Using a simple surfactant‐assisted method, controllable hybridization of TiO2 NTs with conductive amorphous carbon species is realized. The obtained C‐TiO2 NTs is ingeniously chosen to serve as an ideal "vessel" for protein immobilization and biosensor applications. Results show that the appropriate hybridization of C into TiO2 NTs leads to a much better conductivity of TiO2 NTs without destroying their preponderant tubular structures or damaging their excellent biocompatibility and hydrophilicity. When used in loading proteins, the C‐TiO2 NTs can be used as a super vessel for rapid and substantive immobilization of hemoglobin (Hb), with a large surface electroactive Hb coverage (Γ∗︁) of 3.3×10−9 mol·cm−2. Enhanced DET of Hb is commendably observed on the constructed Hb/C‐TiO2 NTs biosensor with a couple of well‐defined redox peaks in a fast electron transfer process. The biosensor further exhibits fast response, high sensitivity and stability for the amperometric biosensing of H2O2 with the detection limit as low as 3.1×10−8 mol/L.
Inhibitors of HIV‐1 Integrase‐Human LEDGF/p75 Interaction Identified from Natural Products via Virtual Screening
Authors: Hu Guoping , Li Xi , Li Yaozong , Sun Xianqiang , Liu Guixia , Li Weihua , Huang Jin , Shen Xu , Tang Yun
Published: December 2012

HIV‐1 integrase (IN)‐mediated integration of viral DNA into the host chromosome is an essential step in the virus life cycle. Human lens epithelium‐derived growth factor (LEDGF/p75) has been found to function as a cellular cofactor in this process. The LEDGF/p75‐IN interaction hence represents an attractive target for anti‐HIV therapy. In this study, natural products were virtually screened against the LEDGF/p75 binding pocket of HIV‐1 IN. 24 compounds were selected and obtained from the National Compound Resource Center of China. AlphaScreen assays characterized 8 of these 24 natural products as potent LEDGF/p75‐IN interaction inhibitors. The active compounds whose IC50 values ranged from 0.56 to 14.55 µmol/L could be used as lead compounds for further investigation. This work confirmed that natural products are valuable resources for antiviral drug discovery.
Pyrene Excimer‐based Bis‐triazolyl Pyranoglycoligands as Specific Mercury Sensors
Authors: He Xiaopeng , Xie Juan , Chen Guorong , Chen Kaixian
Published: December 2012

New C3,4‐disubstituted bis‐triazolyl glycoligands that feature a glucosyl or galactosyl scaffold incorporating two pyrenyl groups were synthesized via the CuI‐catalyzed azide‐alkyne 1,3‐dipolar cycloaddition reaction (Cue‐AAC). These compounds exert a major emission band corresponding to that of pyrene excimer and respond specifically to mercury with a markedly quenched fluorescence. The epimeric nature of the pyranoglycosyl scaffold is determined influential toward the selectivity of the sensors.
Stereoselective Total Synthesis of Tubulysin V
Authors: Wang Rui , Tian Ping , Lin Guoqiang
Published: December 2012

The total synthesis of tubulysin V was accomplished in 1.0% overall yield with linear 13 steps. Our synthetic strategy featured the following two reactions. One is zinc‐mediated aza‐Barbier reaction of (R)‐N‐tert‐butanesulfinyl imine 8 with β‐ester group functionalized allylic bromide 9 to afford the chiral homo‐allylic amine (7); the other is to employ the methodology of aqueous indium‐mediated aza‐Barbier reaction previously developed by our group, giving the chiral homo‐allylic amine 13 with high efficiency.
Role of Nitrogen Oxides, Black Carbon, and Meteorological Parameters on the Variation of Surface Ozone Levels at a Tropical Urban Site – Hyderabad, India
Authors: Yerramsetti Venkata Swamy , Gauravarapu Navlur Nikhil , Rapolu Venkanna , Dhulipala N. S. K. Chitanya , Sinha Puna Ram , Srinavasan Shailaja , Anupoju Gangagni Rao
Published: December 2012

In this study, temporal variations of surface ozone (O3) were investigated at tropical urban site of Hyderabad during the year 2009. O3, oxides of nitrogen (NOx = NO + NO2), black carbon (BC), and meteorological parameters were continuously monitored at the established air monitoring station. Results revealed the production of surface O3 from NO2 through photochemical oxidation. Averaged datasets illustrated the variations in ground‐level concentrations of these air pollutants along different time scales. Maximum mean concentrations of O3 (56.75 ppbv) and NOx (8.9 ppbv) were observed in summer. Diurnal‐seasonal changes in surface O3 and NOx concentrations were explicated with complex atmospheric chemistry, boundary layer dynamics, and local meteorology. In addition, nocturnal chemistry of NOx played a decisive role in the formation of O3 during day time. Mean BC mass concentration in winter (10.92 µg m−3) was high during morning hours. Heterogeneous chemistry of BC on O3 destruction and NOx formation was elucidated. Apart from these local observations, long‐range transport of trace gases and BC aerosols were evidenced from air mass back trajectories. Further, statistical modeling was performed to predict O3 using multi‐linear regression method, which resulted in 91% of the overall variance.
Response Surface Modeling of Cu(II) Removal from Electroplating Waste by Adsorption: Application of Box–Behnken Experimental Design
Authors: Turan Nurdan Gamze , Mesci Başak , Ozgonenel Okan
Published: December 2012

The use of kaolinite‐based clay minerals as a low‐cost natural adsorbent for the removal of Cu(II) from electroplating waste leachate was studied. Batch experiments were conducted to determine the effects of varying adsorbent loading, initial pH, adsorbent dosage, and contact time. Box–Behnken design with three variables like initial pH, adsorbent dosage, and contact time at three different levels was studied to identify a significant correlation between the effects of these variables to the amount of Cu(II) adsorbed. The methodology identifies the principal experimental variables, which have the greatest effect on the adsorption process. After optimizing the input variables by using Simplex algorithm, the adsorption of Cu(II) was maximal (99.9% with a maximum (positive) standard deviation of 9.4) at pH 6.24, adsorbent dosage of 0.83 g L−1, and contact time of 97 min, respectively. Furthermore, the experimental values are in good agreement with predicted values, the correlation coefficient and adjusted correlation coefficients were found to be 0.96 and 0.87, respectively.
Pesticides Removal by Filtration over Cactus Pear Leaves: A Cheap and Natural Method for Small‐Scale Water Purification in Semi‐Arid Regions
Authors: Gebrekidan Abraha , Nicolai Hannah , Vincken Liese , Teferi Mekone , Asmelash Tsehaye , Dejenie Tadesse , Zerabruk Samuel , Gebrehiwet Kindeya , Bauer Hans , Deckers Josef , Luis Patricia , De Meester Luc , van der Bruggen Bart
Published: December 2012

This study aims to examine the efficiency of Opuntia ficus‐indica for removing organochlorine pesticides from surface waters. Adsorption properties such as size, dose, and time of O. ficus‐indica for aldrin, dieldrin, and dichlorodiphenyltrichloroethane (DDT) were studied through stirring and column methods. Because of their high affinity and swelling characteristics, dried O. ficus‐indica was studied in stirring while fresh unpeeled O. ficus‐indica was applied in both stirring and column experiments and proved to be well‐suited to column application. Before removing pesticides, the column was flashed with distilled water eliminate the turbidity and smell from fresh unpeeled cactus. The removal of pesticides increased with an increasing adsorbent dose and decreased with adsorbent particle sizes. The optimum adsorbent dose is 10 g for dried and 15 g for fresh unpeeled O. ficus‐indica. The experimental results show that O. ficus‐indica possesses strong adsorption ability for aldrin, dieldrin, and DDT, and the adsorption isotherm data obeyed the Freundlich model. The results of our small‐scale experiments suggest a strong potential to develop local small‐scale water treatment units that can be used at the level of individual households or local communities, using a widely available adsorbent.
Mn‐citrate and Mn‐HIDA: intermediate‐affinity chelates for manganese‐enhanced MRI
Authors: Seo Yoshiteru , Satoh Keitaro , Morita Hironobu , Takamata Akira , Watanabe Kazuto , Ogino Takashi , Hasebe Tooru , Murakami Masataka
Published: December 2012

In this study we investigated two manganese chelates in order to improve the image enhancement of manganese‐enhanced MRI and decrease the toxicity of free manganese ions. Since both MnCl2 and a low‐affinity chelate were associated with a slow continuous decrease of cardiac functions, we investigated intermediate‐affinity chelates: manganese N‐(2‐hydroxyethyl)iminodiacetic acid (Mn‐HIDA) and Mn‐citrate. The T1 relaxivity values for Mn‐citrate (4.4 m m−1 s−1) and Mn‐HIDA (3.3 m m−1 s−1) in artificial cerebrospinal fluid (CSF) were almost constant in a concentration range from 0.5 to 5 m m at 37 °C and 4.7 T. In human plasma, the relaxivity values increased when the concentrations of these Mn chelates were decreased, suggesting the presence of free Mn2+ bound with serum albumin. Mn‐HIDA and Mn‐citrate demonstrated a tendency for better contractility when employed with an isolated perfused frog heart, compared with MnCl2. Only minimal changes were demonstrated after a venous infusion of 100 m m Mn‐citrate or Mn‐HIDA (8.3 µmol kg−1 min−1) in rats and a constant heart rate, arterial pressure and sympathetic nerve activity were maintained, even after breaking the blood–brain barrier (BBB). Mn‐citrate and Mn‐HIDA could not cross the intact BBB and appeared in the CSF, and then diffused into the brain parenchyma through the ependymal layer. The responses in the supraoptic nucleus induced by the hypertonic stimulation were detectable. Therefore, Mn‐citrate and Mn‐HIDA appear to be better choices for maintaining the vital conditions of experimental animals, and they may improve the reproducibility of manganese‐enhanced MRI of the small nuclei in the hypothalamus and thalamus. Copyright © 2012 John Wiley & Sons, Ltd.
Detection of vascular cell adhesion molecule‐1 expression with USPIO‐enhanced molecular MRI in a mouse model of cerebral ischemia
Authors: Fréchou M. , Beray‐Berthat V. , Raynaud J.‐S. , Mériaux S. , Gombert F. , Lancelot E. , Plotkine M. , Marchand‐Leroux C. , Ballet S. , Robert P. , Louin G. , Margaill I.
Published: December 2012

Vascular damage plays a critical role after stroke, leading notably to edema, hemorrhages and stroke recurrence. Tools to characterize the vascular lesion are thus a real medical need. In this context, the specific nanoparticular contrast agent P03011, an USPIO (ultrasmall superparamagnetic iron oxide) conjugated to a peptide that targets VCAM‐1 (vascular cell adhesion molecule‐1), was developed to detect this major component of the vascular inflammatory response. This study aimed to make the proof of concept of the capacity of this targeted USPIO to detect VCAM‐1 with MRI after cerebral ischemia in mouse. The time course of VCAM‐1 expression was first examined by immunohistochemistry in our model of cerebral ischemia–reperfusion. Secondly, P03011 or nontargeted USPIO P03007 were injected 5 h after ischemia (100 µmol iron kg−1; i.v.) and in vivo and ex vivo MRI were performed 24 h after ischemia onset. Double labeling immunofluorescence was then performed on brain slices in order to detect both USPIO and VCAM‐1. VCAM‐1 expression was significantly up‐regulated 24 h after ischemia in our model. In animals receiving P03011, both in vivo and ex vivo MRI performed 24 h after ischemia onset showed hypointense foci which could correspond to iron particles. Histological analysis showed a co‐localization of the targeted USPIO and VCAM‐1. This study demonstrates that VCAM‐1 detection is possible with the USPIO P03011 in a model of cerebral ischemia. This kind of contrast agent could be an interesting clinical tool to characterize ischemic lesions in terms of vascular damage. Copyright © 2012 John Wiley & Sons, Ltd.
In vivo quantitative assessment of cell viability of gadolinium or iron‐labeled cells using MRI and bioluminescence imaging
Authors: Guenoun Jamal , Ruggiero Alessandro , Doeswijk Gabriela , Janssens Roel C. , Koning Gerben A. , Kotek Gyula , Krestin Gabriel P. , Bernsen Monique R.
Published: December 2012

In cell therapy, noninvasive monitoring of in vivo cell fate is challenging. In this study we investigated possible differences in R1, R2 or R2* relaxation rate as a measure of overall cell viability for mesenchymal stem cells labeled with Gd‐liposomes (Gd‐MSCs) or iron oxide nanoparticles (SPIO‐MSCs). Cells were also transduced with a luciferase vector, facilitating a correlation between MRI findings and cell viability using bioluminescence imaging (BLI). Viable Gd‐MSCs were clearly distinguishable from nonviable Gd‐MSCs under both in vitro and in vivo conditions, clearly differing quantitatively (ΔR1 and ΔR2) as well as by visual appearance (hypo‐ or hyperintense contrast). Immediately post‐injection,viable Gd‐MSCs caused a substantially larger ΔR2 and lower ΔR1 effect compared with nonviable MSCs. With time, the ΔR1 and ΔR2 relaxation rate showed a good negative correlation with increasing cell number following proliferation. Upon injection, no substantial quantitative or visual differences between viable and nonviable SPIO‐MSCs were detected. Moreover, nonviable SPIO‐MSCs caused a persisting signal void in vivo, compromising the specificity of this contrast agent. In vivo persistence of SPIO particles was confirmed by histological staining. A large difference was found between SPIO‐ and Gd‐labeled cells in the accuracy of MR relaxometry in assessing the cell viability status. Gd‐liposomes provide a more accurate and specific assessment of cell viability than SPIO particles. Viable Gd cells can be differentiated from nonviable Gd cells even by visual interpretation. These findings clearly indicate Gd to be the favourable contrast agent in qualitative and quantitative evaluation of labeled cell fate in future cell therapy experiments. Copyright © 2012 John Wiley & Sons, Ltd.
Ovarian cancer
Authors: Kohn Elise C. , Hurteau Jean
Published: December 2012

The field of ovarian cancer research has made marked progress in better understanding ovarian cancer and redefining its types. New information is putting into doubt that mutations in KRAS and/or BRAF always portend poor outcome, at least not in low‐grade serous ovarian cancers.
18F‐Fluorodeoxyglucose positron emission tomography/computed tomography for the detection of recurrent bone and soft tissue sarcoma
Authors: Al‐Ibraheem Akram , Buck Andreas K. , Benz Matthias R. , Rudert Maximilian , Beer Ambros J. , Mansour Asem , Pomykala Kelsey L. , Haller Bernhard , Juenger Hendrik , Scheidhauer Klemens , Schwaiger Markus , Herrmann Ken
Published: December 2012

BACKGROUND:

The clinical utility of modern hybrid imaging modalities for detecting recurrent bone or soft tissue sarcoma remains to be determined. In this report, the authors present a clinical study on the diagnostic accuracy and incremental value of integrated 18F‐fluorodeoxyglucose positron emission tomography/computed tomography (18F‐FDG PET/CT) in patients with a history of sarcoma who have clinically suspected disease recurrence.

METHODS:

Forty‐three patients who had a history of bone or soft tissue sarcoma and had documented complete remission underwent 18F‐FDG PET/CT. Image analysis was performed independently for 18F‐FDG PET (n = 43) and for contrast‐enhanced spiral CT (CE‐CT) (n = 30) by 2 separate readers, whereas combined 18F‐FDG PET/CT (n = 43) images were analyzed in consensus by both readers. Imaging findings were rated on a 5‐point scale and finally were reported as malignant, benign, or equivocal. Imaging findings were validated either by histopathology (n = 24) or by clinical follow‐up (n = 19).

RESULTS:

18F‐FDG PET/CT had greater sensitivity and specificity compared with CE‐CT alone (94% and 92% vs 78% and 67%, respectively), resulting in significantly greater accuracy (93% vs 73%; P = .03). 18F‐FDG PET/CT was particularly superior regarding detection of local recurrence or soft tissue lesions (sensitivity and specificity: 83% and 100% vs 50% and 100%, respectively) or bone metastases (100% and 100% vs 85% and 88%, respectively).

CONCLUSIONS:

18F‐FDG PET/CT had greater diagnostic accuracy in the detection of recurrent bone or soft tissue sarcoma compared with CE‐CT alone. The detection of local recurrence was the most evident advantage of 18F‐FDG PET/CT over CE‐CT. Cancer 2013. © 2012 American Cancer Society.
Neural pathways mediating control of reproductive behavior in male Japanese quail
Authors: Wild J. Martin , Balthazart Jacques
Published: December 2012

The sexually dimorphic medial preoptic nucleus (POM) in Japanese quail has for many years been the focus of intensive investigations into its role in reproductive behavior. The present study delineates a sequence of descending pathways that finally reach sacral levels of the spinal cord housing motor neurons innervating cloacal muscles involved in reproductive behavior. We first retrogradely labeled the motor neurons innervating the large cloacal sphincter muscle (mSC) that forms part of the foam gland complex (Seiwert and Adkins‐Regan [1998] Brain Behav Evol 52:61–80) and then putative premotor nuclei in the brainstem, one of which was nucleus retroambigualis (RAm) in the caudal medulla. Anterograde tracing from RAm defined a bulbospinal pathway, terminations of which overlapped the distribution of mSC motor neurons and their extensive dorsally directed dendrites. Descending input to RAm arose from an extensive dorsomedial nucleus of the intercollicular complex (DM‐ICo), electrical stimulation of which drove vocalizations. POM neurons were retrogradely labeled by injections of tracer into DM‐ICo, but POM projections largely surrounded DM, rather than penetrated it. Thus, although a POM projection to ICo was shown, a POM projection to DM must be inferred. Nevertheless, the sequence of projections in the male quail from POM to cloacal motor neurons strongly resembles that in rats, cats, and monkeys for the control of reproductive behavior, as largely defined by Holstege et al. ([1997], Neuroscience 80:587–598). J. Comp. Neurol. 521:2067–2087, 2013. © 2012 Wiley Periodicals, Inc.
Expression patterns of Pax6 and Pax7 in the adult brain of a urodele amphibian, Pleurodeles waltl
Authors: Joven Alberto , Morona Ruth , González Agustín , Moreno Nerea
Published: December 2012

Expression patterns of Pax6, Pax7, and, to a lesser extent, Pax3 genes were analyzed by a combination of immunohistochemical techniques in the central nervous system of adult specimens of the urodele amphibian Pleurodeles waltl. Only Pax6 was found in the telencephalon, specifically the olfactory bulbs, striatum, septum, and lateral and central parts of the amygdala. In the diencephalon, Pax6 and Pax7 were distinct in the alar and basal parts, respectively, of prosomere 3. The distribution of Pax6, Pax7, and Pax3 cells correlated with the three pretectal domains. Pax7 specifically labeled cells in the dorsal mesencephalon, mainly in the optic tectum, and Pax6 cells were the only cells found in the tegmentum. Large populations of Pax7 cells occupied the rostral rhombencephalon, along with lower numbers of Pax6 and Pax3 cells. Pax6 was found in most granule cells of the cerebellum. Pax6 cells also formed a column of scattered neurons in the reticular formation and were found in the octavolateral area. The rhombencephalic ventricular zone of the alar plate expressed Pax7. Dorsal Pax7 cells and ventral Pax6 cells were found along the spinal cord. Our results show that the expression of Pax6 and Pax7 is widely maintained in the brains of adult urodeles, in contrast to the situation in other tetrapods. This discrepancy could be due to the generally pedomorphic features of urodele brains. Although the precise role of these transcription factors in adult brains remains to be determined, our findings support the idea that they may also function in adult urodeles. J. Comp. Neurol. 521:2088–2124, 2013. © 2012 Wiley Periodicals, Inc.
Composing and scheduling service‐oriented applications in time‐triggered distributed real‐time Java environments
Authors: Estévez‐Ayres Iria , Basanta‐Val Pablo , García‐Valls Marisol
Published: December 2012

During the last decade, the number of distributed application domains with temporal requirements has significantly augmented, arising the necessity of exploring new concepts and paradigms that allow, on the one hand, the development of dynamic and flexible distributed applications and, on the other hand, the reusability of code. Service‐oriented paradigms have been successfully applied to distributed environments, increasing their flexibility and allowing the reusability of their components. Besides, distributed real‐time Java technologies have shown to be a good candidate to deploy real‐time distributed applications. This paper presents a model for service‐oriented applications on a time‐triggered distributed real‐time Java environment, focusing on the definition of the temporal model of an application and its schedulability, applying and evaluating this model in real‐time service‐oriented composition algorithms. Copyright © 2012 John Wiley & Sons, Ltd.
Implementing Evidence‐Based Practice for Patients with Chronic Fatigue Syndrome
Authors: Wiborg Jan F. , Wensing Michel , Tummers Marcia , Knoop Hans , Bleijenberg Gijs
Published: December 2012

The aim of our study was to explore whether community‐based mental health care centres (MHCs) are able to implement and sustain cognitive behaviour therapy (CBT) for chronic fatigue syndrome (CFS) with the help of an implementation manual. We monitored the implementation process and treatment outcome data of three Dutch MHCs that implemented or sustained CBT for CFS, one in the context of a stepped care programme. We compared these data with findings of other treatment studies conducted in the context of CBT for CFS. All three MHCs included at least 40 patients with dropout rates between 15% and 35% from intention‐to‐treat to second assessment. Effect sizes ranged between 0.88 and 1.76 for changes in fatigue severity and 0.43 and 1.23 for changes in physical functioning. With one exception, these outcomes were within the range of our benchmark. Contrary to original expectations, we provided additional implementation support to the two MHCs new with CBT for CFS. We concluded that our implementation manual does not seem to substitute external support for team leaders and associated professions during initial implementation of CBT for CFS but may have the potential to make this assistance more efficient. Particular attention should be paid to challenges of implementing stepped care for CFS. Copyright © 2012 John Wiley & Sons, Ltd.

Key Practitioners Message:

Implementation of CBT for CFS in community‐based MHCs was monitored.

External support was provided in addition to an implementation manual during initial implementation of CBT for CFS.

Participating MHCs were generally capable of successfully implementing and delivering CBT for CFS.

Implementation of low‐intensity interventions for CFS might better be postponed until therapists have sufficient experience with conventional CBT for CFS.
Slit/Robo‐mediated chemorepulsion of vagal sensory axons in the fetal gut
Authors: Goldberg David , Borojevic Rajka , Anderson Monique , Chen Jason J. , Gershon Michael D. , Ratcliffe Elyanne M.
Published: December 2012

COVER PHOTOGRAPH: Fetal mouse gut at E14. Nuclei are illuminated via bisbenzimide fluorescence (blue). Primary antibodies have been omitted; non‐specific immunofluorence can be seen from the application of secondary donkey anti‐goat antibodies labeled with Alexa 488 (green) and goat anti‐chicken antibodies labeled with Alexa 594 (red). From Goldberg et al., Developmental Dynamics 242:9–15.
Transposon mediated BAC transgenesis via pronuclear injection of mouse zygotes
Authors: Rostovskaya Maria , Naumann Ronald , Fu Jun , Obst Mandy , Mueller Doris , Stewart A. Francis , Anastassiadis Konstantinos
Published: December 2012

Pronuclear microinjection of bacterial artificial chromosomes (BACs) is the preferred way to generate transgenic mice because the transgene accurately recapitulates expression of the endogenous gene. However, the method is demanding and the integrity and copy number of the BAC transgene is difficult to control. Here, we describe a simpler pronuclear injection method that relies on transposition to introduce full‐length BACs into the mouse genome. The bacterial backbone of a hPAX6‐GFP reporter BAC was retrofitted with PiggyBac transposon inverted terminal repeats and co‐injected with PiggyBac transposase mRNA. Both the frequency of transgenic founders as well as intact, full‐length, single copy integrations were increased. Transposition was determined by a rapid PCR screen for a transpositional signature and confirmation by splinkerette sequencing to show that theBACs were integrated as a single copy either in one or two different genomic sites. BAC transposons displayed improved functional accuracy over random integrants as evaluated by expression of the hPAX6‐GFP reporter in embryonic neural tube and absence of ectopic expression. This method involves less work to achieve increased frequencies of both transgenesis and single copy, full‐length integrations. These advantages are not only relevant to rodents but also for transgenesis in all systems. genesis 51:135–141, 2013. © 2012 Wiley Periodicals, Inc.
Immunoregulation through membrane proteins modified by reducing conditions induced by immune reactions
Authors: Stegmann Monika , Metcalfe Clive , Barclay A. Neil
Published: December 2012

Selected disulfide bonds in membrane proteins are labile and are thus susceptible to changes in redox potential and/or the presence of thiol isomerase enzymes. Modification of these disulfide bonds can lead to conformational changes of the protein that in turn may alter protein activity and function. This occurs in the entry of several enveloped viruses into their host cells, e.g. HIV, hepatitis C virus and Newcastle disease virus. Labile disulfide bonds are also important in platelet activation, cytokine signalling and in a variety of diseases including cancer and arthritis. In this review we will concentrate on recent advances in understanding the conditions that lead to disulfide bond reduction in membrane proteins and their effects in regulating immune function.
Crucial Influence of the Intramolecular Hydrogen Bond on the Coordination Mode of RC(S)NHP(S)(OiPr)2 in Homoleptic Complexes with NiII
Authors: Babashkina Maria G. , Safin Damir A. , Srebro Monika , Kubisiak Piotr , Mitoraj Mariusz P. , Bolte Michael , Garcia Yann
Published: December 2012

Reaction of the deprotonated N‐thiophosphorylated thioureas RC(S)NHP(S)(OiPr)2 [R = EtNH (HLI), iPrNH (HLII), Et2N (HLIII), 2,5‐Me2C6H3NH (HLIV), 4‐Me2NC6H4NH (HLV)] with NiII leads to complexes of the formula [NiLI–V2]. The molecular structures of the complexes in the solid were elucidated by single‐crystal X‐ray diffraction analysis. In the complexes, the metal atom is found to be in a square‐planar trans‐N2S2 ([NiLII,IV2]) environment formed by the C=S sulfur atoms and the P–N nitrogen atoms, or in a square‐planar trans‐S2S′2 ([NiLI,III2]) environment formed by the C=S and P=S sulfur atoms of two deprotonated ligands. Reaction of deprotonated N‐thiophosphorylated thiourea HLV with NiCl2 leads to violet [Ni(L‐1,3‐N,S)2] or dark violet [Ni(L‐1,5‐S,S′)2]·(CH3)2C=O crystals that were isolated by recrystallization from a mixture of CH2Cl2 or acetone, respectively, and n‐hexane. DFT calculations confirmed that the [Ni(LI,II,IV,V‐N,S)2] conformers are more stable (by 5–7 kcal/mol) than [Ni(LI,II,IV,V‐S,S′)2], whereas [Ni(LIII‐N,S)2] is less stable (by 7–9 kcal/mol) than [Ni(LIII‐S,S′)2]. The main reason for higher stability of the 1,3‐N,S versus 1,5‐S,S′ isomers is the formation of intramolecular N–H···S=P hydrogen bonds. The same hydrogen bonds are impossible in complex [NiLIII2]. In solution, complex [NiLIII2] has revealed an exclusively 1,5‐S,S′ coordination, whereas compounds [NiLI,II,IV,V2] reveal at least two isomers in the 1H and 31P{1H} NMR spectra. The major species is assigned to the 1,3‐N,S‐coordinated isomer, and the minor signals are assigned to the 1,5‐S,S′ isomer, which was confirmed by UV/Vis spectroscopic results. The electrochemical measurements reveal reversible one‐electron reduction and irreversible oxidations both assigned to ligand‐centred processes. Ligand‐based oxidation processes agree well with TD‐DFT results.
Alkaloids from the Sponge‐Associated Fungus Aspergillus sp.
Authors: Zhou Yaming , Debbab Abdessamad , Mándi Attila , Wray Victor , Schulz Barbara , Müller Werner E. G. , Kassack Matthias , Lin WenHan , Kurtán Tibor , Proksch Peter , Aly Amal H.
Published: December 2012

Seven new alkaloids including tryptoquivaline K (1) and fumiquinazolines K–P (2–7), bearing a rare 1‐aminocyclopropane‐1‐carboxylic acid residue, together with six known compounds (8–13), were isolated from the fungus Aspergillus sp. obtained from the Mediterranean sponge Tethya aurantium. The structures of the new compounds were determined by extensive analysis by 1D and 2D NMR spectroscopy and mass spectrometry. The absolute configurations of tryptoquivaline K (1) and fumiquinazolines K and L (2, 3) were determined by TDDFT ECD calculations of their solution conformers, and the configurational assignment of the related fumiquinazolines M–P (4–7) was achieved by comparison of their ECD spectra with those of compounds 2 and 3. All compounds were evaluated for their cytotoxic activity by the MTT method. Compound 8 exhibited pronounced cytotoxicity against the mouse lymphoma cell line (L5178Y) with an IC50 value of 3.6 μM, but only moderate activity was observed against human ovarian cancer (A2780) and human Philadelphia chromosome‐positive chronic myelogenous leukemia (K562) cell lines with IC50 values of 18.5 and 15.0 μM, respectively.
Nanodiamond Decorated with Silver Nanoparticles as a Sensitive Film Modifier in a Jeweled Electrochemical Sensor: Application to Voltammetric Determination of Thioridazine
Authors: Shahrokhian Saeed , Hosseini Nassab Niloufar
Published: December 2012

Nanodiamondgraphite (NDG) decorated with Ag nanoparticles (AgNPs‐NDG) was prepared and used to construct a novel sensitive sensor for the voltammetric determination of thioridazine (TR). The results indicate a remarkable increase in the oxidation peak currents together with a negative shift in the oxidation peak potentials, in comparison to the bare pyrolytic graphite electrode. Remarkable enhancement in microscopic area of the electrode along with strong adsorption of TR on the surface of the modified electrode resulted in a considerable increase in the peak current of TR. The surface morphology and the nature of the composite film deposited on PGE were characterized by scanning electron microscopy, atomic force microscopy, cyclic voltammetry and electrochemical impedance spectroscopy. Experimental variables, such as the deposited amount of the modifier suspension, pH of the supporting electrolyte, the accumulation potential and time are optimized by monitoring the CV responses of TR. Under the optimal conditions, the modified electrode showed a wide linear response to the concentration of TR in the range of 0.08–100 µM with a detection limit of 0.01 µM. The prepared modified electrode showed several advantages: simple preparation method, high stability and uniformity in the composite film, high sensitivity, long‐term stability and remarkable voltammetric reproducibility in response to TR. The modified electrode can be successfully applied for accurate determination of trace amounts of TR in pharmaceutical and clinical preparations.
Carbon Nanotube, Carbon Black and Copper Nanoparticle Modified Screen Printed Electrodes for Amino Acid Determination
Authors: Carvalho Ricardo C. , Mandil Adil , Prathish Krishna P. , Amine Aziz , Brett Christopher M. A.
Published: December 2012

Screen‐printed electrodes have been used for the determination of amino acids, focussing particularly on tryptophan, following different surface modifications by carbon nanotubes (CNT), carbon black (CB) and copper nanoparticles. The modified electrodes were characterised by cyclic voltammetry, electrochemical impedance spectroscopy and scanning electron microscopy. Detection by square wave voltammetry was improved by further surface modification with copper nanoparticles, exhibiting efficient electrocatalytic activity towards amino acid oxidation with high sensitivity, stability and long shelf‐life. The applicability of a low‐cost, robust carbon black substrate using the synergetic electrocatalytic effect provided by copper nanoparticles for amino acid sensing is demonstrated.
Enhanced Anodic Electrochemiluminescence from Co2+‐Doped CdSe Nanocrystals for Alkaline Phosphatase Assay
Authors: Wang Jing , Zhang Yan‐Yan , Zhao Wei‐Wei , Xu Jing‐Juan , Chen Hong‐Yuan
Published: December 2012

Co2+ doped CdSe nanocrystals (CdSe:Co NCs) have been synthesized via a co‐precipitation method in homogeneous solutions. The anodic electrochemiluminescence (ECL) of CdSe:Co NCs with tripropylamine (TPrA) as co‐reactant was studied in aqueous solution for the first time. Co2+ doped IIVI NCs systems exhibit strong coupling due to Co d‐orbital mixing with the valence band and conduction band of the IIVI host, which causes a ca. 3‐fold enhancement in ECL intensity compared with the undoped CdSe NCs. Benefiting from the strong anodic ECL emission of the doped NCs, we developed an alkaline phosphatase (ALP)‐responsive ECL system to detect the enzymatic processes successfully. An inhibition type anodic ECL strategy has been used to sensitively detect ALP ranging from 0.5 nM to 10 nM, with a detection limit of 0.1 nM.