bluuebunny/crossref_metadata_2025 huggingface dataset:
Bayesian nonparametric hierarchical modeling
Authors: Dunson David B.
Published: April 2009

In biomedical research, hierarchical models are very widely used to accommodate dependence in multivariate and longitudinal data and for borrowing of information across data from different sources. A primary concern in hierarchical modeling is sensitivity to parametric assumptions, such as linearity and normality of the random effects. Parametric assumptions on latent variable distributions can be challenging to check and are typically unwarranted, given available prior knowledge. This article reviews some recent developments in Bayesian nonparametric methods motivated by complex, multivariate and functional data collected in biomedical studies. The author provides a brief review of flexible parametric approaches relying on finite mixtures and latent class modeling. Dirichlet process mixture models are motivated by the need to generalize these approaches to avoid assuming a fixed finite number of classes. Focusing on an epidemiology application, the author illustrates the practical utility and potential of nonparametric Bayes methods.
Some contributions to the analysis of multivariate data
Authors: Bathke Arne C. , Harrar Solomon W. , Rauf Ahmad M.
Published: April 2009

In this paper, we provide an overview of recently developed methods for the analysis of multivariate data that do not necessarily emanate from a normal universe. Multivariate data occur naturally in the life sciences and in other research fields. When drawing inference, it is generally recommended to take the multivariate nature of the data into account, and not merely analyze each variable separately. Furthermore, it is often of major interest to select an appropriate set of important variables. We present contributions in three different, but closely related, research areas: first, a general approach to the comparison of mean vectors, which allows for profile analysis and tests of dimensionality; second, non‐parametric and parametric methods for the comparison of independent samples of multivariate observations; and third, methods for the situation where the experimental units are observed repeatedly, for example, over time, and the main focus is on analyzing different time profiles when the number p of repeated observations per subject is larger than the number n of subjects.
Simvastatin impairs smad-3 phosphorylation and modulates transforming growth factor β1-mediated activation of intestinal fibroblasts
Authors: Burke J P , Watson R W G , Murphy M , Docherty N G , Coffey J C , O'Connell P R
Published: April 2009

Background

Transforming growth factor (TGF) β1, acting through the smad pathway, is critical to fibroblast-mediated intestinal fibrosis. Simvastatin exhibits antifibrotic properties. This study assessed the effects of simvastatin on TGF-β1-mediated intestinal fibroblast activation.

Methods

Human intestinal fibroblasts were activated with TGF-β1 with or without simvastatin or the cholesterol pathway intermediates farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). Collagen-Iα2 expression was assessed by reverse transcriptase–polymerase chain reaction. Connective tissue growth factor (CTGF) and smad phosphorylation were evaluated by western blot, and plasminogen activator inhibitor (PAI) 1 activity by enzyme-linked immunosorbent assay. Fibroblast filamentous (F)-actin accumulation was assessed by confocal microscopy and contraction by a fibroblast-populated collagen lattice (FPCL) model.

Results

TGF-β1 treatment of fibroblasts induced smad-2/3 phosphorylation, CTGF and collagen-Iα2 production, F-actin bundling, FPCL contraction and PAI-1 activation. Pretreatment with simvastatin inhibited the induction of CTGF and collagen-Iα2, PAI-1 activation, F-actin bundling and FPCL contraction. The inhibitory effect of simvastatin on PAI-1 activation was reversed by GGPP and FPP. Simvastatin pretreatment inhibited TGF-β1-mediated phosphorylation of smad-3.

Conclusion

Simvastatin abrogates TGF-β1-mediated intestinal fibroblast activation by inhibition of smad-3 phosphorylation. These findings offer a mechanism for the antifibrotic effects of simvastatin and a therapeutic entry point in the treatment of intestinal fibrosis.
Effect of individual fat areas on early surgical outcomes after open gastrectomy for gastric cancer
Authors: Tokunaga M , Hiki N , Fukunaga T , Ogura T , Miyata S , Yamaguchi T
Published: April 2009

Background

Obesity is generally considered a risk factor for postoperative morbidity following open gastrectomy. Body mass index (BMI) is widely accepted as an indicator of obesity, but does not necessarily reflect the distribution of fat. It is unclear how different types of fat may affect the operative procedure and outcome.

Methods

The relationship between fat area (total, visceral and subcutaneous fat, and BMI) and early surgical outcomes (bleeding, operating time, morbidity, hospital death and hospital stay) was investigated in 135 patients who had a curative gastrectomy at the Cancer Institute Hospital, Tokyo, in 2006.

Results

Postoperative intra-abdominal infection, which occurred in 13 patients (9·6 per cent), correlated strongly with visceral (P = 0·023) and total (P = 0·037) fat area. Visceral fat area also correlated with hospital death (P = 0·041) and a longer hospital stay (P = 0·001). Subcutaneous fat area and BMI did not correlate with these early surgical outcomes.

Conclusion

Patients with a high visceral fat area are more likely to develop an intra-abdominal infection after gastrectomy. Assessment of fat area, in particular visceral fat area, should alert surgeons to increased postoperative risks.
Development and validation of an HPLC method to quantify 3,4‐dideoxyglucosone‐3‐ene in peritoneal dialysis fluids
Authors: Frischmann Matthias , Spitzer Johanna , Fünfrocken Michael , Mittelmaier Stefan , Deckert Melanie , Fichert Thomas , Pischetsrieder Monika
Published: April 2009

A method was developed and validated to quantify 3,4‐dideoxyglucosone‐3‐ene in peritoneal dialysis fluids by high‐performance liquid chromatography with UV detection after derivatization with o‐phenylenediamine. The advantages of this method compared with direct HPLC analysis are (i) the possibility of quantifying 3,4‐dideoxyglucosone‐3‐ene simultaneously together with other glucose degradation products, (ii) the compatibility of the method with MS detection for unequivocal identification of the analyte and (iii) a bathochromic shift of the UV absorbance maximum which leads to higher selectivity. The validated method was used to measure 3,4‐dideoxyglucosone‐3‐ene concentrations additionally to the glucose degradation products 3‐deoxyglucosone, methylglyoxal, glyoxal, 5‐hydroxymethylfurfural, 2‐furaldehyde, formaldehyde and acetaldehyde in 19 commercial products for peritoneal dialysis. Copyright © 2009 John Wiley & Sons, Ltd.
A validated HPLC‐fluorescence method with a semi‐micro column for routine determination of homocysteine, cysteine and cysteamine, and the relation between the thiol derivatives in normal human plasma
Authors: Ichinose Saori , Nakamura Mayumi , Maeda Mayu , Ikeda Rie , Wada Mitsuhiro , Nakazato Mio , Ohba Yoshihito , Takamura Noboru , Maeda Takahiro , Aoyagi Kiyoshi , Nakashima Kenichiro
Published: April 2009

A semi‐micro column HPLC‐fluorescence method for routine determination of thiol derivatives such as homocysteine (Hcy), cysteine (Cys) and cysteamine (CA) is described. The thiol derivatives labeled with ammonium‐7‐fluorobenzo‐2‐oxa‐1,3‐diazole‐4‐sulfonate (SBD‐F) were isocratically separated within 12 min on a semi‐micro ODS column (Daisopak‐SP‐120‐5‐ODS‐BP) with a mixture of 25 mm acetate buffer (pH 2.00) and CH3CN as a mobile phase. The purity and similarity of SBD‐thiols by a multi‐wavelength fluorescence detector were more than 92.3 and 96.7%. The detection limits of Hcy, Cys and CA at a signal‐to‐noise ratio of 3 were 0.16, 0.47 and 0.03 µm, respectively. Furthermore validation parameters such as accuracy, precision and robustness of the proposed method showed satisfactory results. Almost 850 plasma sample injections (range 572–1076, n = 3) for a column could be performed without differences in retention time and peak heights of labels. As an application of the proposed method, the determination of thiol derivatives in normal human plasma (n = 103) was demonstrated. The correlation coefficients between Hcy vs Cys and Hcy vs CA were 0.38 and −0.35, respectively. Copyright © 2009 John Wiley & Sons, Ltd.
Validation of a high‐performance liquid chromatography method for the determination of (−)‐α‐bisabolol from particulate systems
Authors: Pedro André São , Detoni Cássia , Ferreira Domingos , Cabral‐Albuquerque Elaine , Sarmento Bruno
Published: April 2009

A reversed‐phase high performance liquid chromatography method has been developed and validated for determination and quantitation of the natural sesquiterpene (−)‐α‐bisabolol. Furthermore the application of the method was done by characterization of chitosan milispheres and liposomes entrapping Zanthoxylum tingoassuiba essential oil, which contains appreciable amount of (−)‐α‐bisabolol. A reversed‐phase C18 column and gradient elution was used with the mobile phase composed of (A) acetonitrile–water–phosphoric acid (19:80:1) and (B) acetonitrile. The eluent was pumped at a flow rate of 0.8 mL/min with UV detection at 200 nm. In the range 0.02–0.64 mg/mL the assay showed good linearity (R2 = 0.9999) and specificity for successful identification and quantitation of (−)‐α‐bisabolol in the essential oil without interfering peaks. The method also showed good reproducibility, demonstrating inter‐day and intra‐day precision based on relative standard deviation values (up to 3.03%), accuracy (mean recovery of 100.69% ± 1.05%) and low values of detection and quantitation limits (0.0005 and 0.0016 mg/mL, respectively). The method was also robust for showing a recovery of 98.81% under a change of solvent in standard solutions. The suitability of the method was demonstrated by the successful determination of association efficiency of the (−)‐α‐bisabolol in chitosan milispheres and liposomes. Copyright © 2009 John Wiley & Sons, Ltd.
Liquid chromatography–mass spectrometry for the simultaneous determination of the catalpol‐related iridoid glucosides, verproside, isovanilloylcatalpol, catalposide and 6‐O‐veratroyl catalpol in rat plasma
Authors: Park Eun Jeong , Oh Sei‐Ryang , Lee Hyeong‐Kyu , Lee Hye Suk
Published: April 2009

Verproside, isovanilloylcatalpol, catalposide and 6‐O‐veratroyl catalpol are bioactive iridoid glucosides isolated from in a number of folk medicinal plants. A rapid, sensitive and selective liquid chromatography/mass spectrometric (LC/MS) method for the simultaneous determination of verproside, isovanilloylcatalpol, catalposide and 6‐O‐veratroyl catalpol in rat plasma was developed. The analytes were extracted from 50 µL of rat plasma with ethyl acetate using 7‐carboxymethyloxy‐3',4',5‐trimethoxyflavone as internal standard and analyzed on an X‐Bridge C18 column within 6.5 min with 40% methanol in 10 mm ammonium formate (pH 3.0). The analytes were quantified using an electrospray ionization mass spectrometry in the selected ion monitoring mode. The standard curves were linear over the concentration ranges of 10–2000 ng/mL for verproside, isovanilloylcatalpol and catalposide and 20–2000 ng/mL for 6‐O‐veratroyl catalpol. The coefficients of variation and relative errors of verproside, isovanilloylcatalpol, catalposide and 6‐O‐veratroyl catalpol for intra‐ and inter‐assay at four quality control levels were 2.5–8.0 and–4.0–6.6%, respectively. This method was successfully applied to the pharmacokinetic study of verproside and its possible metabolite isovanilloylcatalpol after intravenous administration of verproside, a candidate anti‐asthma drug, in male Sprague–Dawley rats. Copyright © 2009 John Wiley & Sons, Ltd.
Determination of zearalenone by liquid chromatography/tandem mass spectrometry and application to a pharmacokinetic study
Authors: Shin Beom Soo , Hong Seok Hyun , Hwang Sang Wook , Kim Hyoung Jun , Lee Jong Bong , Yoon Hae‐Seong , Kim Do Jung , Yoo Sun Dong
Published: April 2009

Zearalenone, a mycotoxin biosynthesized by various Fusarium fungi, is widely found as a contaminant in grains and animal feeds. This study describes a rapid and sensitive LC/MS/MS assay method for the quantification of zearalenone in rat serum. The assay was validated to demonstrate the specificity, linearity, recovery, lower limit of quantification (LLOQ), accuracy and precision. The multiple reaction monitoring was based on the transition of m/z 317.0 → 130.9 for zearalenone and 319.0 → 204.8 for zearalanone (internal standard). The assay utilized a single liquid–liquid extraction with t‐butyl methyl ether and isocratic elution, and the LLOQ was 0.5 ng/mL using 0.1 mL rat serum. The assay was linear over a concentration range from 0.5 to 200 ng/mL, with correlation coefficients >0.9996. The mean intra‐ and inter‐day assay accuracy was 101.2–112.9 and 96.3–108.0%, respectively. The mean intra‐ and inter‐day precision was between 1.3–7.6 and 3.6–10.6%, respectively. The developed assay was applied to a pharmacokinetic study after a bolus intravenous injection of zearalenone in rats. Copyright © 2009 John Wiley & Sons, Ltd.
Homogeneous Catalysts with a Mechanical (“Machine‐like”) Action
Authors: Swiegers Gerhard F. , Huang Junhua , Brimblecombe Robin , Chen Jun , Dismukes G. Charles , Mueller‐Westerhoff Ulrich T. , Spiccia Leone , Wallace Gordon G.
Published: April 2009

Molecular machines? The factors involved in and the fundamental nature of a “mechanical” action within molecular catalysis is explored in detail. Such mechanical homogeneous catalysts are rare but not unknown (see graphic). The spatial and temporal nature of their catalytic action is considered. Potential implications for mimicry of enzymes are discussed.

magnified image

Chemical reactions may be controlled by either: 1) the minimum threshold energy that must be overcome during collisions between reactant molecules/atoms (the activation energy, Ea), or: 2) the rate at which reactant collisions occur (the collision frequency, A)—for reactions with low Ea. Reactions of type 2 are governed by the physical, mechanical interaction of the reactants. Such mechanical processes are unusual, but not unknown in molecular catalysts. In this work we examine the machine‐like nature of the action in various abiological mechanical catalysts and consider the implications for mimicry of biological catalysts.
Die Welt wird flacher. Beitrag der Chemie zum flachen Fernseher
Authors: Römer Michael , Becker Werner
Published: April 2009

Schneller, schärfer, größer – und immer weiter verbreitet – so lässt sich die Erfolgsgeschichte der LC‐Displays beschreiben. Das Geheimnis dahinter: High‐Tech‐Flüssigkristalle mit ganz besonderen Eigenschaften, die die leichten, energiesparenden LCDs erst ermöglichen. Moderne Kommunikation ist durch sie erst mobil und sichtbar geworden. Seit Jahren ist Merck weltweit Technologie‐ und Marktführer auf dem Gebiet der Flüssigkristalle, deren Mischungen und Anwendungen.
Theoretical considerations on small color differences ascribed to the standard observer made on the basis of individual color‐matching functions
Authors: Carreño Fernando , Ezquerro José Miguel , Zoido Jesús M.
Published: April 2009

An analytical method to determine how color‐matching functions influence the perception of chromaticity differences is proposed. We show that, as a consequence of the observer metamerism, a metameric color‐match perceived by one observer may appear to be a significant mismatch to a different observer. It is also shown that, on average, the differences between the color‐matchings made by two different observers can be estimated to be in the order of 2 CIELAB units. © 2009 Wiley Periodicals, Inc. Col Res Appl, 34, 194–200, 2009
Effect of Halide and Acid Additives on the Direct Synthesis of Hydrogen Peroxide using Supported Gold–Palladium Catalysts
Authors: Ntainjua N. Edwin , Piccinini Marco , Pritchard James C. , Edwards Jennifer K. , Carley Albert F. , Moulijn Jacob A. , Hutchings Graham J.
Published: April 2009

Acidity is crucial: The effect of halide and acid addition on the direct synthesis of hydrogen peroxide is studied for magnesium oxide‐ and carbon‐supported bimetallic gold–palladium catalysts. When using a Au–Pd/C catalyst, the acidity of the methanol/water solvent has a profound effect on the productivity (P).

magnified image

The effect of halide and acid addition on the direct synthesis of hydrogen peroxide is studied for magnesium oxide‐ and carbon‐supported bimetallic gold–palladium catalysts. The addition of acids decreases the hydrogenation/decomposition of hydrogen peroxide, and the effect is particularly pronounced for the magnesium oxide‐supported catalysts whilst for carbon‐supported catalysts the pH requires close control to optimize hydrogen peroxide synthesis. The addition of bromide leads to a marked decrease in the hydrogenation/decomposition of hydrogen peroxide with either catalyst. These effects are discussed in terms of the structure of the gold–palladium alloy nanoparticles and the isoelectric point of the support. We conclude that with the highly active carbon‐supported gold–palladium catalysts these additives are not required and that therefore this system presents the potential for the direct synthesis of hydrogen peroxide to be operated using green process technology.
Dust Charging in Space‐related Laboratory Experiments: A Review Focused on Secondary Emission
Authors: Pavlů J. , Šafránková J. , Němeček Z. , Richterová I.
Published: April 2009

A role of dust in the space environment is of increasing interest in the recent years. Also the fast development of fusion devices with magnetic confinement brought new issues in the plasma‐surface interaction. While there is a number of dusty plasma reviews, the present paper surveys experimental results connected with charging of dust grains under well‐defined laboratory conditions for both space and industrial applications. The main purpose of these experiments is to study particular charging/discharging processes preferably on spacerelated (i.e., all sorts of glass and other oxides) as well as on elemental materials (carbon, nickel, gold). Single micrometer‐sized spherical grains or grain's clusters stored in vacuum are exposed to electron and ion beams. Among several charging processes, the secondary emission is discussed in broad details because this process plays a prominent role everywhen a portion of energetic electrons is present in the medium surrounding a particular grain (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Dual transgene strategy for live visualization of chromatin and plasma membrane dynamics in murine embryonic stem cells and embryonic tissues
Authors: Nowotschin Sonja , Eakin Guy S. , Hadjantonakis Anna‐Katerina
Published: April 2009

To simultaneously follow multiple subcellular characteristics, for example, cell position and cell morphology, in living specimens requires multiple subcellular labels. Toward this goal, we generated dual‐tagged mouse embryonic stem (ES) cells constitutively expressing differentially localized, spectrally distinct, genetically encoded fluorescent protein fusions. We have used human histone H2B fusions to fluorescent proteins to mark chromatin. This provides a descriptor of cell position, division, and death. An additional descriptor of cell morphology is achieved by combining this transgene with select lipid‐modified fluorescent protein fusions that mark the plasma membrane. Using this strategy, wewere able to live image cellular dynamics in three dimensions over time both in cultured ES cells and in mouse embryos generated using dual‐tagged ES cells. This study, therefore, presents the feasibility of applying multiple spectrally and subcellularly distinct fluorescent protein reporters for live imaging studies in ES cells and mouse embryos. Furthermore, the increasing availability of spectral variant fluorescent proteins along with the development of methods that permit improved spectral separation now facilitate multiplexing of fluorescent reporters to provide readouts of a variety of anatomical and physiological behaviors simultaneously in living specimens. genesis 47:330–336, 2009. © 2009 Wiley‐Liss, Inc.
Generation of red fluorescent protein transgenic dogs
Authors: Hong So Gun , Kim Min Kyu , Jang Goo , Oh Hyun Ju , Park Jung Eun , Kang Jung Taek , Koo Ok Jae , Kim Teoan , Kwon Mo Sun , Koo Bon Chul , Ra Jeong Chan , Kim Dae Yong , Ko CheMyong , Lee Byeong Chun
Published: April 2009

Dogs (Canis familiaris) share many common genetic diseases with humans and development of disease models using a transgenic approach has long been awaited. However, due to the technical difficulty in obtaining fertilizable eggs and the unavailability of embryonic stem cells, no transgenic dog has been generated. Canine fetal fibroblasts were stably transfected with a red fluorescent protein (RFP) gene‐expressing construct using retrovirus gene delivery method. Somatic cell nuclear transfer was then employed to replace the nucleus of an oocyte with the nucleus of the RFP‐fibroblasts. Using this approach, we produced the first generation of transgenic dogs with four female and two male expressing RFP. genesis 47:314–322, 2009. © 2009 Wiley‐Liss, Inc.
Attention‐deficit hyperactivity symptoms and disorder in eating disorder inpatients
Authors: Yates William R. , Lund Brian C. , Johnson Craig , Mitchell Jeff , McKee Patrick
Published: April 2009

Objective:

The objective of this study was to determine the prevalence of attention‐deficit hyperactivity disorder (ADHD) symptoms and a DSM‐IV ADHD diagnosis in women admitted for treatment of an eating disorder.

Method:

One hundred eighty‐nine inpatient women with an eating disorder were interviewed using the Structured Clinical Interview for DSM‐IV Axis I Disorders (SCID‐I) and ADHD interview from the Multi‐international Psychiatric Interview (MINI).

Results:

Twenty‐one percent of the sample reported at least six current ADHD symptoms, but the estimated prevalence rate for a diagnosis of ADHD in this population was only 5.8% (95% CI: 2.6%–9.5%). Most current ADHD inattentive symptoms appeared after childhood suggesting late‐onset non‐ADHD origins. Current inattention symptoms in those without a diagnosis of ADHD correlated with higher BMI (p < .0001), symptoms of bulimia nervosa and current level of depression symptoms (p = .025).

Discussion:

Although current ADHD symptoms were commonly endorsed in this population, clinicians should carefully examine for childhood symptom‐onset of ADHD. © 2008 by Wiley Periodicals, Inc. Int J Eat Disord 2009
Single‐Crystal Structure Determination and Solid‐State NMR Investigations of Lithium Nitridosilicate Li2SiN2 Synthesized by a Precursor Approach Employing Amorphous “Si(CN2)2” (Eur. J. Inorg. Chem. 12/2009)
Authors: Pagano Sandro , Zeuner Martin , Hug Stephan , Schnick Wolfgang
Published: April 2009

The cover picture shows the [SiN2]2– framework of the lithium ion conductor Li2SiN2. The hitherto unknown crystal structure reveals possible Li+ pathways (red channels) for lithium ion conductivity. Li2SiN2 was synthesized from “Si(CN2)2”, highlighted as a promising precursor for nitridosilicates in arc‐welded (top left) tantalum crucibles. The structure was solved from single crystals, and the 7Li MAS solid‐state NMR spectrum (bottom right) is presented. Details are discussed in the article by W. Schnick et al. on p. 1579 ff.
Preparation of Fused Tetracyclic Quinazolinones by Combinations of Aza‐Wittig Methodologies and CuI‐Catalysed Heteroarylation Processes
Authors: Bleda Juan Antonio , Fresneda Pilar M. , Orenes Raul , Molina Pedro
Published: April 2009

A number of linear quinazolinones fused to five‐membered rings – benzimidazo[2,1‐b]quinazolinones 8 and benzothiazolo[2,3‐b]quinazolinones 10 – have been prepared from iminophosphoranes 4, derived from N‐substituted o‐azidobenzamides by a combination of the aza‐Wittig methodology and CuI‐catalysed heteroarylation. The presence of a nitrogen functionality in the N‐aryl substituent of 4 promotes heterocyclization after an aza‐Wittig reaction/reductive process, either across the 2‐position, to afford quinazolino[2,1‐b]quinazolinones 11–14, or across the 4‐position, to afford the benzimidazo[1,2‐c]quinazoline 16 from the initially formed 3H‐quinazolin‐4‐one. When an acetyl group is present in the N‐aryl substituent of 4, aza‐Wittig reactions with isocyanates lead directly to 4‐methylene‐4H‐3,1‐benzoxazines 18; this transformation involves the initial formation of a carbodiimide, which undergoes ring‐closure through the enol form of the carboxamide group and eventually an unprecedented iminobenzoxazine/methylenebenzoxazine rearrangement. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Autoregressive models for maxima and their applications to CH4and N2O
Authors: Toulemonde Gwladys , Guillou Armelle , Naveau Philippe , Vrac Mathieu , Chevallier Frederic
Published: April 2009

Recordings of daily, weekly, or yearly maxima in environmental time series are classically fitted by the generalized extreme value (GEV) distribution that originates from the well‐established extreme value theory (EVT). One special case of such GEV distribution is the Gumbel family which corresponds to the modeling of maxima stemming from light‐tailed distributions. To capture temporal dependencies, linear autoregressive (AR) processes offer a simple and elegant framework. Our objective is to extend linear AR models in such a way that they handle Gumbel distributed maxima. To reach this goal, we take advantage of the stability of Gumbel random variables when added to the logarithm of a positive α‐stable random variable. This allows us to propose a linear Gumbel distributed AR model whose main theoretical properties are derived. For the atmospheric scientist, this link between linear AR processes and EVT widens the statistical treatment of extreme environmental recordings in which temporal dependencies are present. For example, our model is fitted to daily and weekly maxima of methane (CH4) and daily maxima of nitrous oxide (N2O) measured in Gif‐sur‐Yvette (France). Simulation results are also presented in order to assess the quality of our parameter estimations for finite samples. Copyright © 2009 John Wiley & Sons, Ltd.
Functional connectivity in the default network during resting state is preserved in a vegetative but not in a brain dead patient
Authors: Boly M. , Tshibanda L. , Vanhaudenhuyse A. , Noirhomme Q. , Schnakers C. , Ledoux D. , Boveroux P. , Garweg C. , Lambermont B. , Phillips C. , Luxen A. , Moonen G. , Bassetti C. , Maquet P. , Laureys S.
Published: April 2009

Recent studies on spontaneous fluctuations in the functional MRI blood oxygen level‐dependent (BOLD) signal in awake healthy subjects showed the presence of coherent fluctuations among functionally defined neuroanatomical networks. However, the functional significance of these spontaneous BOLD fluctuations remains poorly understood. By means of 3 T functional MRI, we demonstrate absent cortico‐thalamic BOLD functional connectivity (i.e. between posterior cingulate/precuneal cortex and medial thalamus), but preserved cortico‐cortical connectivity within the default network in a case of vegetative state (VS) studied 2.5 years following cardio‐respiratory arrest, as documented by extensive behavioral and paraclinical assessments. In the VS patient, as in age‐matched controls, anticorrelations could also be observed between posterior cingulate/precuneus and a previously identified task‐positive cortical network. Both correlations and anticorrelations were significantly reduced in VS as compared to controls. A similar approach in a brain dead patient did not show any such long‐distance functional connectivity. We conclude that some slow coherent BOLD fluctuations previously identified in healthy awake human brain can be found in alive but unaware patients, and are thus unlikely to be uniquely due to ongoing modifications of conscious thoughts. Future studies are needed to give a full characterization of default network connectivity in the VS patients population. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Inhibition of mammalian target of rapamycin signaling potentiates the effects of all‐trans retinoic acid to induce growth arrest and differentiation of human acute myelogenous leukemia cells
Authors: Nishioka Chie , Ikezoe Takayuki , Yang Jing , Gery Sigal , Koeffler H. Phillip , Yokoyama Akihito
Published: April 2009

Our study explored the drug interaction of all‐trans retinoic acid (ATRA) and RAD001 (everolimus), the inhibitor of mammalian target of rapamycin complex 1 (mTORC1), in acute myelogenous leukemia (AML) NB4 and HL60 cells. RAD001 (10 nM) significantly enhanced the ATRA‐induced growth arrest and differentiation of these cells, as measured by colony‐forming assay and cell cycle analysis, and expression of CD11b cell surface antigen and nitroblue tetrazolium reduction, respectively. ATRA (0.1–1 μM) upregulated levels of RTP801, a negative regulator of mTORC1, and inhibited mTORC1 signaling as assessed by measurement of the levels of p‐p70S6K and p‐4E‐BP1 in HL60 and NB4 cells. ATRA (0.1–1 μM) in combination with RAD001 (10 nM) strikingly downregulated the levels of p‐70S6K and p‐4E‐BP1 without affecting the total amount of these proteins. Notably, RAD001 (10 nM) significantly augmented ATRA‐induced expression of CCAAT/enhancer‐binding protein ε (C/EBPε) and p27kip1 and downregulated levels of c‐Myc in these cells. Furthermore, RAD001 (5 mg/kg) enhanced the ability of ATRA (10 mg/kg) to inhibit the proliferation of HL60 cells growing as tumor xenografts in immune‐deficient nude mice. Taken together, concomitant blockade of the RA and mTORC1 signaling may be a promising treatment strategy for individuals with AML. © 2009 UICC
HLA‐DR expression is associated with better prognosis in sporadic Australian clinicopathological Stage C colorectal cancers
Authors: Walsh Michael D. , Dent Owen F. , Young Joanne P. , Wright Caroline M. , Barker Melissa A. , Leggett Barbara A. , Bokey Les , Chapuis Pierre H. , Jass Jeremy R. , Macdonald Graeme A.
Published: April 2009

Predicting patient outcome for colorectal carcinoma (CRC) with lymph node but not distant metastases remains challenging. Various prognostic markers have been identified including microsatellite instability (MSI) and possibly expression of the MHC Class II protein, HLA‐DR. About 15% of sporadic CRC exhibits MSI associated with methylation of the DNA mismatch repair gene hMLH1 promoter. In addition, a significant proportion of unselected CRC demonstrates expression of HLA‐DR. We sought to examine the relationship between HLA‐DR expression, MSI status and prognosis in sporadic Australian Clinicopathological (ACP) Stage C CRC. Two hundred seventy consecutive patients with sporadic ACP Stage C CRC were treated at Concord Repatriation General Hospital between 1986 and 1992. None of these patients received adjuvant chemotherapy and all were followed for a minimum of 5 years or until death. DNA was extracted from paraffin sections and MSI status determined by PCR. HLA‐DR expression was determined immunohistochemically using an antibody against the HLA‐DR α chain. MSI status could be assigned in 235 cases: 176 CRCs (74.9%) were microsatellite stable, whereas 23 (9.8%) had high levels of MSI (MSI‐H) and 36 (15.3%) had low levels of MSI (MSI‐L). HLA‐DR expression by CRC cells was seen in 148 (60.1%) cases and correlated with the presence of tumor‐infiltrating lymphocytes (p = 0.0005) and peritumoral lymphocytes (p = 0.003), but not other clinicopathological features or MSI status. HLA‐DR‐positive CRCs were strongly associated with better patient outcome (p < 0.0001). © 2009 UICC
Testing for cointegration using the Johansen approach: are we using the correct critical values?
Authors: Turner Paul
Published: April 2009

This paper presents Monte Carlo simulations for the Johansen cointegration test which indicate that the critical values applied in a number of econometrics software packages are inappropriate. This is due to confusion in the specification of the deterministic terms included in the vector error correction model (VECM). The result is a tendency to reject the null of no cointegration too often. Copyright © 2009 John Wiley & Sons, Ltd.
Are dispersal‐dependent behavioral traits produced by phenotypic plasticity?
Authors: Meylan Sandrine , de Fraipont Michèle , Aragon Pedro , Vercken Elodie , Clobert Jean
Published: April 2009

Dispersal is a common response to deteriorating conditions such as intense competition, food limitation, predation or parasitism. Although it provides obvious advantages, dispersal is often assumed to be costly. Selection is therefore likely to have acted to decrease these costs, and indeed several studies demonstrated that dispersers and philopatric individuals differ in their morphology, physiology and/or behavior. Using the common lizard (Lacerta vivipara) as our model system, we examined the contribution of phenotypic plasticity to the establishment of dispersal‐dependent behavioral traits. We used a reciprocal transplant experiment in which conditions at the maternal site of origin, during offspring development in utero, and at the release site were manipulated. We then compared activity, social interactions and foraging behavior between individuals that stayed philopatric and those that dispersed. Most behavioral traits were also measured at birth and after the dispersal phase.

This study demonstrates that (a) 10 months after the dispersal phase, there were still marked behavioral differences between dispersing and philopatric individuals, (b) the reaction when confronted to another individual was also dispersal‐status dependent, a result which strongly suggests that individuals are able to recognize the dispersal status of same‐age conspecifics and (c) none of the behavioral characteristics were found to be dependent on the environmental conditions (maternal and natal environment) indicating a lack of phenotypic plasticity in the building of the dispersal‐dependent behavioral traits examined. J. Exp. Zool. 311A:377–388, 2009. © 2009 Wiley‐Liss, Inc.
The synthesis and chemistry of a bis‐pyrazolinylketone and the structure determination
Authors: Lin Tay‐Yean , Cromwell Norman H. , Kingsbury Charles A.
Published: April 2009

The synthesis and spectral characteristics of a bis‐spiro compound: 2,6‐bis(4‐phenyl‐3‐δ1‐pyrazolinyl)cyclo‐hexanone are reported. Unlike literature reports, this particular δ1‐pyrazoline does not readily rearrange to the 2 isomer on heating. Pyrolysis gives 2,6‐bis(α‐methylbenzylidene)cyclohexanone. A monopyrazolinylket‐one was also isolated which is most likely an intermediate in the bis‐denitrogenation. A mechanism for the denitrogenation‐rearrangement is proposed.
Synthesis of heterocyclic compounds. XXXIX. Synthesis of 5‐cyano‐2‐phenyl‐4‐thioxo‐3,4‐dihydropyrimidines
Authors: Lorente A. , García Navío J. L. , Vaquero J. J. , Soto J. L.
Published: April 2009

The reaction of thiobenzamide with 3‐alkoxy‐3‐aryl(or alkyl)‐2‐cyanopropenenitriles 1 and sodium 2‐propoxide in 2‐propanol afforded after acidic treatment 6‐aryl(or alkyl)‐5‐cyano‐2‐phenyl‐4‐thioxo‐3,4‐dihydropyrimidines 3 through formation of the 3‐aryl(or alkyl)‐2‐cyano‐3‐thiobenzamidopropenenitrile 2 that has been isolated in one case (2a, R1 = Ph).
Synthesis of 7‐oxopyrrolo[3,2‐B]pyridine‐6‐carboxylic acid derivatives as potential antimicrobial agents
Authors: Bayomi Said M. , Price Kenneth E. , Sowell J. Walter
Published: April 2009

A route for the synthesis of various derivatives of 7‐oxopyrrolo[3,2‐b]pyridine‐6‐carboxylic acid from 2‐methyl‐3‐carbomethoxy‐4‐aminopyrrole is reported.
Synthesis of 4,10‐dihydro‐4,10‐dioxo‐1H[1]benzothiopyrano[3,2‐B]pyridine and 7‐oxo‐7,13‐dihydro[1]benzothiopyrano[2,3‐b]‐1,5‐benzodiazepine
Authors: Nakazumi Hiroyuki , Endo Takashi , Nakaue Toshiyuki , Kitao Teijiro
Published: April 2009

3‐Amino‐4H‐1‐benzothiopyran‐4‐one (3‐aminothiochromone) was easily prepared by reaction of 3‐bromo‐thiochromen‐4‐one with sodium azide in methanol‐water. Condensation of 3‐aminothiochromone with diethyl ethoxymethylenemalonate and with dimethyl acetylenedicarboxylate gave intermediates, which were thermally cyclized to give 4,10‐dihydro‐4,10‐dioxo‐1H[1]benzothiopyrano[3,2‐b]pyridinecarboxylates. 3‐Formyl‐thiochromone was condensed with o‐phenylenediamine to give 7‐oxo‐7,13‐dihydro[1]benzothiopyrano[2,3‐b]‐1,5‐benzodiazepine.
Synthesis using pyridinium anhydrobases, preparation of indolizine derivatives
Authors: Molina P. , Fresneda P. M. , Lájara M. C.
Published: April 2009

A number of derivatives of indolizine ring system have been prepared from 1‐substituted 4,6‐diphenyl‐2‐phenacylidene‐1,2‐dihydropyridines either by metallation with LDA or acylation and further basic treatment. Similarly, I‐arylmethyl‐4,6‐diphenyl‐2‐dicyanomethylene‐1,2‐dihydropyridines by action of LDA undergo cyclization to the corresponding 2‐amino‐1‐cyano‐3‐aryl indolizines.
Synthesis of 2‐(2‐imidazolinyl) substituted 2,3‐dihydro‐4H‐1,4‐benzothiazine and 3,4‐dihydro‐2H‐1,4‐benzoxazines
Authors: Butler Richard C. M. , Chapleo Christopher B. , Myers Peter L. , Welbourn Anthony P.
Published: April 2009

An investigation into the synthesis of benzoxazine, benzoxathiane and benzothiazine derivatives of 2‐(2‐imidazolinyl)‐1,4‐benzodioxane has been carried out.
Novel nucleophilic substitution of alkyl bromo‐2(1H)‐pyridones
Authors: Pessolano A. A. , Witzel B. E. , Graham P. M. , Clark R. L. , Jones H. , Dorn C. P. , Carty J. , Shen T. Y.
Published: April 2009

Nucleophilic substitution of certain alkyl bromo‐2(1H)‐pyridones gave some unexpected products where the alkyl group is substituted and the ring bromine is replaced by hydrogen. The expected ring substituted product is also formed, but only as the minor product in most cases. Many reactions are cited with various nucleophiles, and a plausible mechanism is also presented.
E‐ and Z‐isomerism of 2‐acetylthiophene oximes
Authors: Conde Santiago , Corral Carlos , Lissavetzky Jaime
Published: April 2009

A study on the oximation of a number of 2‐acetylthiophenes in order to ascertain the validity of contradictory results previously described is reported. The fact that the steric hindrance is smaller in 2‐acetylthiophenes unsubstituted at position‐3 than in acetylbenzenes allows in these cases the formation of Z oximes, which even can predominate on the E oximes in the case of a + M substitution at position‐5. In the paper is also shown that the E/Z ratio of 2‐acetylthiophene oximes can be deduced from the 1H‐nmr spectrum of the crude oxime mixture.
Substituted 2‐Pyrones and 5,6‐Dihydropyrones
Authors: Groutas William C. , Huang Tien L. , Stanga Michael A. , Brubaker Michael J. , Moi Min K.
Published: April 2009

A series of substituted 2‐pyrones and 5,6‐dihydropyrones have been synthesized and investigated for their inhibitory activity toward human leukocyte elastase, procine pancreatic elastase and chymotrypsin.
Electron impact induced fragmentation of some 7‐(o‐ and p‐R‐benzylidene)‐3‐(o‐ and p‐R‐phenyl)‐3,3a,4,5,6,7‐hexahydro‐2H‐indazoles. I
Authors: Cortés E. , Martínez R. , Arzacoya E.
Published: April 2009

The mass spectral fragmentation patterns of ten 7‐(o‐ and p‐R‐benzylidene)‐3‐(o‐ and p‐R‐phenyl)‐3,3a,4,5,6,7‐hexahydro‐2H‐indazoles, I, obtained by electron impact have been studied. All the spectra analyzed contain molecular ions and the principal fragmentation routes take place either from the molecular ion, or from (M+‐1) ion. Likewise, our investigation of the mass spectra of these compounds revealed interesting relationships between the substitution pattern in the framework of I and the fragmenation pathways.
Synthesis of 2,3,9,10,16,17,23,24‐octaethylphthalocyanine
Authors: Camenzind Mark J. , Hill Craig L.
Published: April 2009

The first preparation of 2,3,9,10,16,17,23,24‐octaethylphthalocyanine (1) and synthetic precursor molecules is described.
Purine analog inhibitors of xanthine oxidase ‐ structure activity relationships and proposed binding of the molybdenum cofactor
Authors: Robins Roland K. , Revankar Ganapathi R. , O'Brien Darrell E. , Springer Robert H. , Albert Thomas Novinson Anthony , Senga Keitaro , Miller Jon P. , Streeter David G.
Published: April 2009

A number of new hypoxanthine analogs have been prepared as substrate inhibitors of xanthine oxidase. Most noteworthy inhibitory new hypoxanthine analogs are 3‐(m‐tolyl)pyrazolo[1,5‐a]pyrimidin‐7‐one (47), ID50 0.06 μM and 3‐phenylpyrazolo[1,5‐a]pyrimidin‐7‐one (46), ID50 0.40 μM. 5‐(p‐Chlorophenyl)pyrazolo[1,5‐a]pyrimidin‐7‐one (63) and the corresponding 5‐nitrophenyl derivative 64 exhibited an ID50 of 0.21 and 0.23 μM, respectively. 7‐Phenylpyrazolo[1,5‐a]‐s‐triazin‐4‐one (40) is shown to exhibit an ID50 of 0.047 μM. The structure‐activity relationships of these new phenyl substituted hypoxanthine analogs are discussed and compared with the xanthine analogs 3‐m‐tolyl‐ and 3‐phenyl‐7‐hydroxypyrazolo[1,5‐a]pyrimidin‐5‐ones (90) and (91), previously reported from our laboratory to have ID50 of 0.025 and 0.038 μM, respectively. The presence of the phenyl and substitutedphenyl groups contribute directly to the substrate binding of these potent inhibitors. This work presents an updated study of structure‐activity relationships and binding to xanthine oxidase. In view of the recent elucidation of the pterin cofactor and the proposed binding of this factor to the molybdenum ion in xanthine oxidase, a detailed mechanism of xanthine oxidase oxidation of hypoxanthine and xanthine is proposed. Three types of substrate binding are viewed for xanthine oxidase. The binding of xanthine to xanthine oxidase is termed Type I binding. The binding of hypoxanthine is termed Type II binding and the specific binding of alloxanthine is assigned as Type III binding. These three types of substrate binding are analyzed relative to the most potent compounds known to inhibit xanthine oxidase and these inhibitors have been classified as to the type of inhibitor binding most likely to be associated with specific enzyme inhibition. The structural requirements for each type of binding can be clearly seen to correlate with the inhibitory activity observed. The chemical syntheses of the new 3‐phenyl‐ and 3‐substituted phenylpyrazolo[1,5‐a]pyrimidines with various substituents are reported. The syntheses of various 8‐phenyl‐2‐substituted pyrazolo‐[1,5‐a]‐s‐triazines, certain s‐triazolo[1,5‐a]‐s‐triazines and s‐triazolo[1,5‐a]pyrimidine derivatives prepared in connection with the present study are also described.
Addition de dérivés maloniques sur des β‐énaminones cycliques
Authors: Bellassoued‐Fargeau Marie‐Claude , Graffe Bernadette , Sacquet Marie‐Claude , Maitte P.
Published: April 2009

L'addition d'acétonitriles activés 6 sur des β‐énaminocétones 5 dérivées de cétones cycliques et benzyliques, en milieu basique (éthylate de sodium ou triton B) est étudiée. Cette réaction conduit à la formation d'α‐py‐rone 8 à l'exclusion du cycle pyridinique. La structure des nouveaux dérivés 8 est établie par rmn et ir.
Synthesis and spectral characterization of some new N‐substituted 2‐aminobenzothiazoles, 2‐aminothiazolopyridines and 2‐aminothiazoloquinolines
Authors: Sarkis George Y. , Faisal Essam D.
Published: April 2009

A series of N‐substituted 2‐aminobenzothiazoles, 2‐aminothiazolopyridines, and 2‐aminothiazoloquinolines were prepared by the cyclization of N,N'‐disubstituted thiourea derivatives by bromine in acetic acid. The uv, ir and nmr data for these compounds are presented and discussed.
Synthèse de nouveaux réactifs génotoxiques, les dérivés nitrés d'anthrafurannes
Authors: Bilger Christine , Demerseman Pierre , Royer René
Published: April 2009

On décrit diverses voies d'accès au formyl‐1 hydroxy‐2 anthracène, au formyl‐2 hydroxy‐1 anthracène et au formyl‐1 hydroxy‐2 méthoxy‐6 anthracène. Ces composés sont employés pour la synthèse des dérivés nitrés sur l'hétérocycle d'anthrafurannes, dans le but de comparer leurs propriétés mutagènes à celles des dérivés nitrés correspondants de naphtofurannes.
The deoxydative substitution reactions of nicotinamide and nicotinic acid N‐oxides by 1‐adamantanethiol in acetic anhydride
Authors: Prachayasittikul Supaluk , Bauer Ludwig
Published: April 2009

The reaction of nicotinamide N‐oxide with 1‐adamantanethiol in acetic anhydride yielded a mixture of 2‐and 6‐(1‐adamantylthio)nicotinamides (49%, in the ratio of 24:1) and 2‐, 5‐, and 6‐(1‐adamantylthio)nicotino‐nitriles (18%, in the ratio of 79:1:20). From a reaction of nicotinic acid N‐oxide with 1‐adamantanethiol, there was isolated 2‐(1‐adamantylthio)nicotinic acid as the only sulfide in 23% yield. Carbonsulfur bond cleavage took place when 2‐(1‐adamantylthio)nicotinic acid, or the corresponding amide or nitrile, were boiled with concentrated hydrochloric acid to furnish 2‐mercaptonicotinic acid and 1‐chloroadamantane, quantitatively. The reaction of nicotinamide N‐oxide alone in acetic anhydride at 135° formed N‐acetyl‐2‐hydroxynicotinamide (61%), 2‐hydroxynicotinonitrile (0.5%) and N,N‐diacetyl‐2‐acetoxynicotinamide (0.8%).
Synthesis and structure of 6‐ and 7‐(acylmethyl)pteridines
Authors: Abdel‐Hady Sayed A. L. , Badawy Mohamed A. , Mosselhi Mosselhi A. N. , Ibrahim Yehia A.
Published: April 2009

6‐(Acylmethyl)‐7‐hydroxypteridines 7‐14 as well as the isomeric 7‐(acylmethyl)‐6‐hydroxypteridines 15‐22 were prepared by condensation of 5,6‐diaminouracils 1 and 2 with ethyl aroylpyruvates 3‐6 in pyridine and hydrochloric acid, respectively. The structures of the newly synthesized compounds were confirmed by their hydrolysis into the 7‐hydroxy‐6‐methyl‐23, 24 and 6‐hydroxy‐7‐methylpteridines 25 and 26. The synthesis of the 2‐(methylthio) derivative 28 is also described.
Synthesis of water soluble 8‐substituted 5‐deazaflavins
Authors: Link P. A J. , Van Der Plas H. C. , Müller F.
Published: April 2009

By oxidative cyclization of 5,5′‐arylmethylenebis(6‐methylaminouracil) derivatives with diethyl azodicarb‐oxylate a number of 5‐deazaisoalloxazines were synthesized having at the C(8) position a substituent that causes a bathochromic shift varying between 20 and 130 nm, depending on the substituent. To increase the solubility in aqueous media 8‐substituted 5‐deazaflavins were prepared having a carboxymethyl group at the N(3) position. The carboxymethyl group was introduced prior to the oxidative cyclization.
Presence of an N‐6 acetate group shifts the alkylation site of the ambident nucleophile sodium 1‐N‐methylisoguanide
Authors: Nachman Ronald J.
Published: April 2009

Inclusion of an N‐6 acetate into the ambident nucleophile, sodium 1‐N‐methylisoguanide, resulted in a shift in alkylation preference from N‐9 to N‐3. The preparation of the N‐6 acetate of 1‐N‐methylisoguanine, 9‐N‐acetyl‐1‐N‐methylisoguanine (4), and related acetate analogs are described and evidence presented for their structural determination. Analysis of long range 13C‐1H coupling data facilitated the structural elucidation of the predominant alkylation products and provided evidence for the unusual N‐7 hydrogen tautomeric form in one of them, 3‐N‐benzyl‐6‐N‐acetyl‐1‐N‐methylisoguanine (8).
Basicity of azoles. VII. Basicity of C‐aminopyrazoles in relation to tautomeric and protonation studies
Authors: Catalán Javier , Menéndez Margarita , Laynez José , Claramunt Rosa María , Bruix Marta , De Mendoza Javier , Elguero José
Published: April 2009

The pKa values of five aminopyrazoles [3(5)‐amino, 1‐methyl‐3‐amino, 1‐methyl‐5‐amino, 4‐amino and 1‐methyl‐4‐amino] were determined. The aqueous basicities are discussed in terms of tautomerism (72% of 3‐amino tautomer), protonation site (only 4‐aminopyrazoles protonate on the amino group) and amino substituent effects. The results of theoretical calculations, carried out at the semiempirical INDO level, indicate that in the gas phase 3‐ and 5‐aminopyrazoles protonate on the pyrazolic nitrogen atom, whereas 4‐aminopyrazoles possess similar proton affinities for both nitrogen atoms (pyrazolic and amino).