bluuebunny/crossref_metadata_2025 huggingface dataset:
Template Effects in SN2 Displacements for the Preparation of Pseudopeptidic Macrocycles
Authors: Martí‐Centelles Vicente , Burguete M. Isabel , Luis Santiago V.
Published: January 2012

Macrocyclisation reactions ofC2‐symmetric pseudopeptides containing central pyridine‐derived spacers are affected by the presence of different anions. The selection of the proper anion gives excellent results for the preparation of the corresponding macrocyclic structures. Kinetic studies show that the presence of those anions enhances both the yield and the rate of the reaction. Computational studies at the B3LYP/6‐31G* level have allowed us to rationalise the experimental results. The obtained transition states (TSs) show that the interaction between the anion and the open‐chain pseudopeptidic chain has a stabilising effect. The anion stabilises the two TSs involved: the first one, which involves the formation of the initial bond between the two subunits and leads to an open‐chain intermediate, and the second one, which precedes the formation of the cyclic structure. The optimum anion (Br−when the central spacer is derived from 2,6‐bis(aminomethyl)pyridine, is able to act as a template, in that it forces the two ends of the open‐chain intermediate to approach each other by forming hydrogen bonds with the two amino acid subunits present in the intermediate. This stabilises the second TS to a greater extent than the first one, and thus, favours macrocyclisation over the competing oligomerisation reactions. The computational calculations also allowed us to predict the outcome of new experiments. Accordingly, the synthesis of the pseudopeptidic macrocycle derived from 2,6‐diaminopyridine was not successful under the optimised conditions previously used. Nevertheless, calculations predicted that in this case Cl−should be more efficient than Br−, and this was subsequently experimentally confirmed. Interestingly, the presence of different substituents on the constituent amino acids seems to play a minor role in the overall process.
A Novel and Simple Molecular Probe Sensing Hg(II) in Living Cells by Chelation‐enhanced Fluorescence
Authors: Meng Qinghua , Cheng Sen , Lan Minbo , Wei Gang
Published: January 2012

Mercury is currently widely used in industries which leads to various means of Hg(II) waste exposure and its accumulation in organisms will cause neurological damages. Thus, there is a great need for the design of probes or sensors with high sensitivity and selectivity for detecting and monitoring Hg(II) at physiological pH. Thus a novel and simple molecular probe P1 was prepared from 1,1′‐(1,3‐phenylene)‐bis(2,4‐pentanedionato) for sensing Hg(II) via chelation‐enhanced fluorescence (CHEF) mechanism. The probe indicated a selectively fluorescent response to Hg(II) in aqueous media excited by the ultraviolet light of 254 nm. The recognition mechanism was further studied by semi‐empirical AM1 and molecular mechanics MM+ methods in HyperChem 8.0. The calculation indicated a tetrahedron coordination geometry for Hg(II) and a chair‐like configuration for the total molecule. The fluorescent images sensing Hg(II) in living mouse fibroblast cells by the probe were obtained by fluorescence microscope.
Chiral (6,3) Network Assembled by Lanthanide and Changeful Dihydroxyfumaric Acid
Authors: Zhang Manbo , Lü Jing , Hu Ruixiang
Published: January 2012

A series of chiral two‐dimensional lanthanide coordination polymers, [Ln2(L)3(H2O)6]n·n/3H2O [Ln=Nd (1a, 1b), Sm (2), Eu (3), Tb (4), Dy (5), Ho (6), Er (7); H2L=2,2‐dihydroxylmalonic acid], have been hydrothermally synthesized by using dihydroxyfumaric acid as a source of polydentate O‐donor ligands. The luminescence behaviors of 3 and 4 have been investigated, and they exhibit strong red and green fluorescence in the visible region respectively.
Synthesis, Antibacterial Activities and Nuclease Properties of Ternary Copper(II) Complex Containing 2‐(2′‐Pyridyl)benzothiazole and Glycinate
Authors: Lu Yanmei , Chen Yongheng , Ou Zhibin , Chen Shi , Zhuang Chuxiong , Le Xueyi
Published: January 2012

A new ternary complex [Cu(PBT)(Gly)(H2O)]ClO4 (PBT=2‐(2′‐pyridyl)benzothiazole, and Gly=glycinate) has been synthesized and characterized by elemental analysis, molar conductivity, and IR methods. The complex, structurally characterized by single‐crystal X‐ray crystallography, shows a slightly distorted square‐pyramidal coordination geometry in which two nitrogen atoms of PBT and the carboxylate oxygen atom O and the amino nitrogen atom N of Gly bind at the basal plane, a water molecule is coordinated at the apical position. The complex, Cu(ClO4)2 and free PBT were each tested for their ability to inhibit the growth of two Gram(−) (Escherichia coil, Salmonella) and two Gram(+) (Bacillus subtilis, Staphylococcus aureus) microorganisms. The complex showed good antibacterial activities against the microorganisms compared with free PBT and Cu(ClO4)2. The interaction between the complex and calf thymus DNA in aqueous solution was investigated using electronic spectroscopy, fluorescence spectroscopy, circular dichroic spectroscopy, and viscosity measurements. Results suggest that the complex could bind to DNA by an intercalative mode. In addition, the result of agarose gel electrophoresis showed that the complex can cleave the plasmid DNA by hydroxyl radicals and singlet oxygen‐like species under the condition of physiological pH and room temperature.
A Rapid and Simple Method for Quantitative Aziridination from Aminobrominated Derivatives of Olefins under Solvent‐free and Mild Conditions
Authors: Wei Junfa , Chen Zhanguo , Gao Yanni , Zhang Peng , Wang Chuanning , Zhao Pengfei , Wang Yun , Shi Xianying
Published: January 2012

The urea‐catalyzed aziridination of 1,2‐vicinal haloamines derived from aminohalogenation of olefins has been developed. This rapid and simple method was carried out by simply grinding the solid mixture of the substrate, K2CO3 and catalytic amount of urea at room temperature in air. The reaction provides a protocol for quantitative preparation of aziridines in a large scope of aminohalogenated derivatives of olefins including α,β‐unsaturated ketones, α,β‐unsaturated esters and simple olefins. The possible mechanism involving an H‐bond promoting deprotonation has been suggested for this reaction.
Recent Advances in the Total Synthesis of Chlorosulfolipids
Authors: Nilewski Christian , Carreira Erick M.
Published: January 2012

First isolated in the late 1960s from microalgae of theOchromonas species, the chlorosulfolipids were largely considered as intractable synthetic challenges until recently. Indeed, only in the last few years has this class of natural products received intense attention from the synthetic community, motivated by the many interdisciplinary questions these entities raise. As a consequence, the numerous synthetic and spectroscopic studies that have appeared have contributed to a better understanding of the chemistry of chlorosulfolipids. More than forty years after their discovery, their mysteries are being revealed through the implementation of synthetic tactics and strategies. This microreview summarizes the progress in the synthesis and study of these fascinating natural products.
Voltammetric Ion‐Selective Nanocomposite Carbon Paste Electrode for Determination of Erbium at the Interface Between two Immiscible Electrolyte Solutions
Authors: Mirshafian R. , Norouzi P. , Ganjali M. R.
Published: January 2012

In this study for the first time a novel erbium(III) voltammetric ion‐selective nanocomposite carbon‐paste electrode was introduced based on the concept of ion transfer at the interface between two immiscible electrolyte solutions. N′‐(2‐hydroxy‐1,2‐diphenylethylidene) benzohydrazide (HDB) was used as a selective ionophore in the composition of the carbon paste. The ionophore facilitates transfer of Er(III) from the aqueous solution to the room temperature ionic liquid (RTIL) phase after reduction of the redox probe to maintain charge neutrality. The plot of the peak potential versus the logarithm of the concentration exhibits a Nernstian response (19.9±0.2 mV decade−1) toward Er(III) in the range of 7.5×10−7–1.0×10−1 mol L−1 with detection limit of 5.0×10−7 mol L−1. The proposed sensor shows a fast response time of about 5 s.
Differential cell proliferation in the cortex of the appsweps1de9 alzheimer's disease mouse model
Authors: Kamphuis Willem , Orre Marie , Kooijman Lieneke , Dahmen Maurice , Hol Elly M.
Published: January 2012

Plaque deposition in Alzheimer's disease (AD) is known to decrease proliferation in neurogenic niches in AD mouse models, but the effects on cell proliferation and differentiation in other brain areas have not been studied in detail. We analyzed cell proliferation in the cortex of wild type (WT) and APPswePS1dE9 transgenic (AD) mice at different ages. Mice were studied shortly after the last BrdU injection (BrdU[ST]). In AD mice, the number of proliferating cells increased fourfold, coinciding with plaque appearance and its associated reactive gliosis and activation of microglia. An increase in the number of BrdU[ST]‐cells expressing markers for activated microglia is underlying the enhanced proliferation. Cortical reactive astrocytes did not become proliferative since BrdU[ST]‐cells were negative for different astrocyte‐specific markers. The number of Olig2‐positive oligodendrocyte precursor cells was unchanged. Four weeks after the last BrdU application, the number of BrdU[LT]‐cells with an activated microglia signature was still enhanced in AD mice. None of the newborn cells had differentiated into oligodendrocytes, astrocytes, or neurons. On the basis of these observations, we conclude that amyloid plaque deposition increases proliferation of microglia around plaques but does not affect the proliferation of cortical oligodendrocyte precursor cells. No evidence was found for damage‐induced proliferation of reactive astrocytes or for a redirected neurogenesis from the subventricular zone. The proliferation of microglia contributes to the rapid accumulation of microglia around plaques and may play a role in limitating plaque expansion. © 2012 Wiley Periodicals, Inc.
AP2 adaptor complex mediates bile salt export pump internalization and modulates its hepatocanalicular expression and transport function
Authors: Hayashi Hisamitsu , Inamura Kaori , Aida Kensuke , Naoi Sotaro , Horikawa Reiko , Nagasaka Hironori , Takatani Tomozumi , Fukushima Tamio , Hattori Asami , Yabuki Takashi , Horii Ikuo , Sugiyama Yuichi
Published: January 2012

The bile salt export pump (BSEP) mediates the biliary excretion of bile salts and its dysfunction induces intrahepatic cholestasis. Reduced canalicular expression of BSEP resulting from the promotion of its internalization is one of the causes of this disease state. However, the molecular mechanism underlying BSEP internalization from the canalicular membrane (CM) remains unknown. We have shown previously that 4-phenylbutyrate (4PBA), a drug used for ornithine transcarbamylase deficiency (OTCD), inhibited internalization and subsequent degradation of cell-surface-resident BSEP. The current study found that 4PBA treatment decreased significantly the expression of α- and μ2-adaptin, both of which are subunits of the AP2 adaptor complex (AP2) that mediates clathrin-dependent endocytosis, in liver specimens from rats and patients with OTCD, and that BSEP has potential AP2 recognition motifs in its cytosolic region. Based on this, the role of AP2 in BSEP internalization was explored further.

In vitro

analysis with 3×FLAG-human BSEP-expressing HeLa cells and human sandwich-culture hepatocytes indicates that the impairment of AP2 function by RNA interference targeting of α-adaptin inhibits BSEP internalization from the plasma membrane and increases its cell-surface expression and transport function. Studies using immunostaining, coimmunoprecipitation, glutathione

S
-transferase pulldown assay, and time-lapse imaging show that AP2 interacts with BSEP at the CM through a tyrosine motif at the carboxyl terminus of BSEP and mediates BSEP internalization from the CM of hepatocytes.

Conclusion:

AP2 mediates the internalization and subsequent degradation of CM-resident BSEP through direct interaction with BSEP and thereby modulates the canalicular expression and transport function of BSEP. This information should be useful for understanding the pathogenesis of severe liver diseases associated with intrahepatic cholestasis.
Prediction of temperature variation within a snowpack in open areas and under different canopy covers
Authors: Altunkaynak Abdüsselam , Aydın Abdurrahim
Published: January 2012

Snow temperature is a major component of many physical processes in a snowpack. The temperature and the change in temperature across a layer have a dominant effect on physical properties of snow grains as well as its hardness, strength, and failure resistance. In this study, temperature and snow cover thickness were measured during the snow season of 2007–2008 in 11 elevation classes and in three different sampling locations, one in an open area and two under different forest canopy covers for each class along Kartalkaya road, Bolu. Each sampling site was visited 44 times to collect data including snow depth, snow surface temperature, ground temperature, and temperature within snowpack at 20‐cm intervals. Seven different models are developed to determine snowpack temperature variations under forest canopy covers and in an open area with different leaf area index values. All models were performed using a multilayer perceptron (MP) method for the Bolu–Kartalkaya area, Turkey. MP approach constitutes a standard form of neural network modeling and can modify two‐layer linear perceptron methods using three and more layers. The ability of MP is to handle complex nonlinear interactions, which ease the natural process of modeling. This method can overcome complex computations using neuron networks, and they can easily nonlinearly link input and output variables. The predictive errors are determined on the basis of mean absolute error and mean square error criteria. The Nash–Sutcliffe sufficiency score showing compliance between observed and predicted values is also calculated. According to the mean absolute error, the mean square error, and the Nash–Sutcliffe sufficiency score criteria, the predictive errors are within reasonable error intervals, justifying the use of the developed MP models for engineering applications. Copyright © 2012 John Wiley & Sons, Ltd.
Loss of gene function as a consequence of human papillomavirus DNA integration
Authors: Schmitz Martina , Driesch Corina , Beer‐Grondke Katrin , Jansen Lars , Runnebaum Ingo B. , Dürst Matthias
Published: January 2012

Integration of the human papillomavirus (HPV) genome into the host chromatin is a characteristic step in cervical carcinogenesis. Integration ensures constitutive expression of the viral oncogenes E6 and E7 which drive carcinogenesis. However, integration has also an impact on host DNA. There is increasing evidence that integration not only occurs in fragile sites and translocation breakpoints but also in transcriptionally active regions. Indeed, a substantial number of integration sites actually disrupt host genes and may thereby affect gene expression. No doubt, even subtle changes in gene expression may influence the cell phenotype but small fold changes are difficult to quantify reliably in biopsy material. We have, therefore, addressed the question whether a complete loss of gene function that is insertional mutagenesis in combination with deletion or epigenetic modification of the second allele is also a phenomenon pertinent to cervical cancer. Out of the ten preselected squamous cell carcinomas analyzed, all viral integration sites were located within the intron sequences of known genes, giving rise to viral–cellular fusion transcripts of sense orientation. Moreover, for two tumors, we provide evidence for complete functional loss of the gene affected by HPV integration. Of particular note is that one of the genes involved is the recently described novel tumor suppressor gene castor zinc finger 1. Although our study provides no functional proof that any of the genes affected by HPV integration are causally involved in the transformation process, an exhaustive systematic look at the role of insertional mutagenesis in cervical cancer appears to be warranted.
The proteolytic activity of MT4‐MMP is required for its pro‐angiogenic and pro‐metastatic promoting effects
Authors: Host Lorin , Paye Alexandra , Detry Benoit , Blacher Silvia , Munaut Carine , Foidart Jean Michel , Seiki Motoharu , Sounni Nor Eddine , Noel Agnès
Published: January 2012

Membrane‐type 4 matrix metalloprotease (MT4‐MMP) expression in breast adenocarcinoma stimulates tumor growth and metastatic spreading to the lung. However, whether these pro‐tumorigenic and pro‐metastatic effects of MT4‐MMP are related to a proteolytic action is not yet known. Through site directed mutagenesis MT4‐MMP has been inactivated in cancer cells through Glutamic acid 249 substitution by Alanine in the active site. Active MT4‐MMP triggered an angiogenic switch at day 7 after tumor implantation and drastically accelerated subcutaneous tumor growth as well as lung colonization in recombination activating gene‐1‐deficient mice. All these effects were abrogated upon MT4‐MMP inactivation. In sharp contrast to most MMPs being primarily of stromal origin, we provide evidence that tumor‐derived MT4‐MMP, but not host‐derived MT4‐MMP contributes to angiogenesis. A genetic approach using MT4‐MMP‐deficient mice revealed that the status of MT4‐MMP produced by host cells did not affect the angiogenic response. Despite of this tumor intrinsic feature, to exert its tumor promoting effect, MT4‐MMP requires a permissive microenvironment. Indeed, tumor‐derived MT4‐MMP failed to circumvent the lack of an host angio‐promoting factor such as plasminogen activator inhibitor‐1. Overall, our study demonstrates the key contribution of MT4‐MMP catalytic activity in the tumor compartment, at the interface with host cells. It identifies MT4‐MMP as a key intrinsic tumor cell determinant that contributes to the elaboration of a permissive microenvironment for metastatic dissemination.
Functional Paracyclophanes: Synthesis of [2.2]Paracyclophanemethyldithiocarbonates Using Thione–Thiol Rearrangement of S,O‐Dithiocarbonates (Benzyl Schönberg Rearrangement) at Mild Conditions
Authors: Frank Daniel , Nieger Martin , Friedmann Christian , Lahann Jörg , Bräse Stefan
Published: January 2012

A pathway to benzylic [2.2]paracyclophane thiol derivatives was investigated using the benzyl Schönberg rearrangement.
The Structures of Three [2.2]Paracyclophane Derivatives with Anellated Four‐Membered Rings
Authors: Hopf Henning , Hinrichs Heino , Ernst Ludger , Jones Peter G. , Boekelheide Virgil
Published: January 2012

The structures of the three benzocyclobutenophanes 1 a, 1 b (2 stereoisomers), and 11 have been determined by NMR spectroscopy and X‐ray structural analysis. The preparation of 11 from 4,5‐diethynyl[2.2]paracyclophane (9) is described.
Diverse sensory inputs permit priming in the acidic saline model of hyperalgesia
Authors: Jasper L.L. , MacNeil B.J.
Published: January 2012

Background

The rodent acidic saline model of hyperalgesia uses repeat injections of acidic saline in the right lateral gastrocnemius muscle, spaced five days apart, to induce a persistent decrease in hindpaw withdrawal thresholds. The objective of this study was to determine if alternate injection sites would permit development of hyperalgesia.

Methods

The location of the first muscle injection was varied between 3 groups of rats to include the right lateral gastrocnemius, the right medial gastrocnemius or the left lateral gastrocnemius. All second injections were placed in the right lateral gastrocnemius.

Results

As reported by others, placing both injections in the right lateral gastrocnemius produced a significant reduction in paw withdrawal thresholds 24 hours after the second injection (p < 0.05). Relocating the first injection to the right medial gastrocnemius or the left lateral gastrocnemius also produced significant reductions in paw withdrawal thresholds (p < 0.05 for both). Hyperalgesia was also observed if the first muscle injection was replaced with a systemic injection of lipopolysaccharide. Further experiments tested whether glia cells may contribute to the priming process. Pretreatment with minocycline prior to the first injection completely blocked the development of hyperalgesia but was ineffective if injected before the second injection.

Conclusions

These data indicate that anatomically diverse peripheral stimuli can converge within the central nervous system to produce hyperalgesia.
Pyrazolones as Building Blocks in Heterocyclic Synthesis: Synthesis of New Pyrazolopyran, Pyrazolopyridazine and Pyrazole Derivatives of Expected Antifungicidal Activity
Authors: Ramiz Mahmoud. M. M. , Hafiz Ibrahim. S. Abdel , Reheim Mohamed. A. M. Abdel , Gaber Hatem M.
Published: January 2012

A series of new pyrazolone and pyrazole derivatives with expected antifungicidal activity have been prepared through the reactions 3‐phenyl‐1‐H‐pyrazol‐5(4H)‐one (3) and 4‐(dimethylaminomethylene)‐3‐phenyl‐1H‐pyrazol‐5(4H)‐one (5) with a variety of electrophilic reagents and nucleophilic reagents. The newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR and mass spectral studies.
Development of Polymeric Resin Ion‐exchanger Based Chloride Ion‐selective Electrode for Monitoring Chloride Ion in Environmental Water
Authors: Cheng Cheanyeh , Huang Zhu‐Ming , Chung Wen‐Yaw , Pijanowskad Dorota G. , Dawgul Marek
Published: January 2012

A chloride ion‐selective electrode (ISE) membrane was developed by using a copolymeric ion‐exchanger resin (trimethyl ethenyl quaternary ammonium chloride polystyrene‐divinylbenzene copolymer resin, TMEQAC PSDVB), the ionophore ({μ‐[4,5‐Dimethyl‐3,6‐bis(dodecyloxy)‐1,2‐phenylene]}bis(mercury chloride), ETH9033), the plasticizer (bis(2‐ethylhexyl) sebacate, DOS), and the membrane substrate (polyvinylchloride, PVC). At 25 °C, the electrode exhibited an ideal Nernstian response of 59.2 mV/decade with the linear calibration concentration range from 1.0 × 10−4‐1.0 × 10−2 M (r2 = 0.9930). The limit of detection was 2.45 ppm (6.9 × 10−2 mM) and the measurement response time was less than 10 seconds. The working temperature range of electrode was 10‐45 °C. The working pH range for chloride ion measurement was 2.0‐11.0. Among the various anions examined in this work, only I−, SCN−, and MnO4− ions show significant interference to the electrode measurement. The chloride ISE can be used at least 72 days. The determination of chloride ion content in three kinds of environmental water sample with the electrode method was accurate (92‐95%) and precise (RSD < 4.4%) and did not show significance difference from the high‐performance liquid chromatography method.
Kinetics of Malachite Green Fading in Water‐ethanol‐1‐propanol Ternary Mixtures
Authors: Samiey Babak , Zafari Mahshid
Published: January 2012

The rate constant of malachite green (MG+) alkaline fading was measured in water‐ethanol‐1‐propanol ternary mixtures. This reaction was studied under pseudo‐first‐order conditions at 283‐303 K. It was observed that the reaction rate constant increases in the presence of different weight percentages of ethanol and 1‐propanol. The fundamental rate constants of MG+ fading in these solutions were obtained by SESMORTAC model. In each series of experiments, concentration of one alcohol was kept constant and the concentration of the second one was changed. It was observed that at constant concentration of one alcohol and variable concentrations of the second one, with increase in temperature, k1 values increase and this indicates that presence of ethanol (or 1‐propanol) increases dissolution of 1‐propanol (or ethanol) in the activated complex formed in these solutions. Also, in each zone, fundamental rate constants of reaction at each certain temperature change as k2 » k1 » k−1.
Kinetics and Protein‐Inhibitor Docking Studies of Enantiomers of exo‐2‐Norbornyl‐N‐n‐butylcarbamates as Pseudomonas Lipase Inhibitors to Probe the Enantioselectivity of the Enzyme
Authors: Shen Yu‐Fang , Lin Gialih
Published: January 2012

The Pseudomonas species lipase inhibition shows enantioselectivity for R‐enantiomer over S‐enantiomer of exo‐2‐norbornyl‐N‐n‐butylcarbamates. R‐, S‐, and racemic‐exo‐2‐norbornyl‐N‐n‐butylcarbamates are all characterized as pseudo substrate inhibitors of the enzyme. Thus, the mechanism for Pseudomonas species lipase‐catalyzed hydrolysis of the inhibitor is formation of the first enzyme‐inhibitor Michaelis complex via nucleophilic attack of the active site serine to the inhibitor (Ki step) then formation of the butylcarbamyl enzyme intermediate from this complex (k2 step). Comparison of bimolecular rate constants (ki = k2 / Ki) of the inhibitors indicates that R‐enantiomer is 1.8 times more potent than S‐enantiomer. Thus, Pseudomonas species lipase shows enantioselectivity of 1.8 for R‐exo‐2‐norbornyl‐N‐n‐butyl‐carbamate over S‐exo‐2‐norbornyl‐N‐n‐butylcarbamate. Protein‐ligand interaction studies on both enantiomers of exo‐2‐norbornyl‐N‐n‐butylcarbamate as inhibitors of Pseudomonas species lipase using AutoDock suggest that R‐enantiomer binds more tightly into the active site of the enzyme than S‐enantiomer. The norbornyl ring of S‐exo‐2‐norbornyl‐N‐n‐butylcarbamate is repulsive to Ser 82 and His 251 of the catalytic triad as well as to Met 16 of the oxyanion hole. These repulsions may create few unfavorable interactions between S‐exo‐2‐norbornyl‐N‐n‐butylcarbamate and the enzyme and make this inhibitor a less potent one.
New Application of Chemically Modified Multiwalled Carbon Nanotubes with Thiosemicarbazide as a Sorbent for Separation and Preconcentration of Trace Amounts of Co(II), Cd(II), Cu(II), and Zn(II) in Environmental and Biological Samples Prior to Determination by Flame Atomic Absorption Spectrometry
Authors: Tavallali Hossein , Abdardideh Dawood , Aalaei Mehdi , Zahmatkesh Saeed
Published: January 2012

The present article reports the application of Thiosemicarbazide‐modified multiwalled carbon nanotubes (MWCNTs‐TSC) as a new, easily prepared selective and stable solid sorbent for the preconcentration of trace Co(II), Cd(II), Cu(II) and Zn(II) ions in aqueous solution prior to the determination by flame atomic absorption spectrometry. The studied metal ions can be adsorbed quantitatively on MMWNTs at pH 5.0 and then eluted completely with HNO3 (1.5 mol L−1) prior to their determination by flame atomic absorption spectrometry. The separation/preconcentration conditions of analytes were investigated, including the pH, the sample flow rate and volume, the elution condition and the interfering ions. The maximum adsorption capacity of the adsorbent at optimum conditions were found to be 32.5, 27.3, 44.5 and 34.1 mg g−1 for Co(II), Cd(II), Cu(II) and Zn(II), and the detection limits of the method were found to be 0.28, 0.13, 0.21 and 0.17 μg L−1, respectively. The proposed method was successfully applied for extraction and determination of the analytes in well water, sea water, wastewater, soil, and blood samples.
In silico analysis of the two tandem somatomedin B domains of ENPP1 reveals hints on the homodimerization of the protein
Authors: Bellacchio Emanuele
Published: January 2012

The homodimerization of ENPP1 is mediated by the two somatomedin B (SMB) domains of the protein through a mechanism that is yet unknown at the atomistic level. The tandem arrangement of these domains without an intermediate spacer implies their possible packing into a functional assembly, which we explored by rigid docking. To exclude potential bias in the docking search we assessed the absence of flexible protein regions by evaluating the normalized B‐factors calculated from the Cα atom displacements derived from molecular dynamics simulations. After filtering the docking results exploiting the criterion that residues located at the inter‐domain interfaces are more conserved than non‐interface residues, the resulting best model of the tandem SMB domains revealed the presence of two large conserved surface patches not engaged in the inter‐domain contact. The largest patch is flat and contains all the invariant positively charged residues characterized by fully solvent‐exposed side chains within the tandem SMB domains, suggesting as a possible role its interaction with the negative phospholipids on the cell surface. We envisage that an ENPP1 monomer bound to the cell membrane via the transmembrane segment can also interact with the cell surface through the largest conserved patch favoring a specific geometry of the tandem SMB module on the cell that optimally exposes the second conserved patch for the symmetric interaction with another membrane‐bound ENPP1 monomer, finally promoting the homodimerization. Biological implications of this model and insights into the effects of the K173Q variant associated with insulin resistance and related abnormalities are presented. J. Cell. Physiol. 227: 3566–3574, 2012. © 2012 Wiley Periodicals, Inc.
Synthesis and bioanalytical evaluation of morphine‐3‐O‐sulfate and morphine‐6‐O‐sulfate in human urine and plasma using LC‐MS/MS
Authors: Andersson Maria , Janosik Tomasz , Shirani Hamid , Slätt Johnny , Fischer Andreas , Beck Olof
Published: January 2012

The aim of this work was to synthesize morphine‐3‐O‐sulfate and morphine‐6‐O‐sulfate for use as reference substances, and to determine the sulfate conjugates as possible heroin and morphine metabolites in plasma and urine by a validated LC‐MS/MS method. Morphine‐6‐O‐sulfate and morphine‐3‐O‐sulfate were prepared as dihydrates from morphine hydrochloride, in overall yields of 41 and 39% with product purities of >99.5% and >98%, respectively. For bioanalysis, the chromatographic system consisted of a reversed‐phase column and gradient elution. The tandem mass spectrometer was operated in the positive electrospray mode using selected reaction monitoring, of transition m/z 366.15 to 286.40. The measuring range was 5–500 ng/mL for morphine‐3‐O‐sulfate and 4.5–454 ng/mL for morphine‐6‐O‐sulfate in plasma. In urine, the measuring range was 50–5000 ng/mL for morphine‐3‐O‐sulfate and 45.4–4544 ng/mL for morphine‐6‐O‐sulfate. The intra‐assay and total imprecision (coefficient of variation) was below 11% for both analytes in urine and plasma. Quantifiable levels of morphine‐3‐O‐sulfate in authentic urine and plasma samples were found. Only one authentic urine sample contained a detectable level of morphine‐6‐O‐sulfate, while no detectable morphine‐6‐O‐sulfate was found in plasma samples.
Characterization of 4,5‐Dihydro‐1H‐Pyrazole Derivatives by 13C NMR Spectroscopy
Authors: Carrión M. Dora , Chayah Mariem , Choquesillo‐Lazarte Duane , Gallo Miguel A. , Espinosa Antonio , Entrena Antonio , Camacho M. Encarnación
Published: January 2012

The 13 C NMR resonances of 19 1‐acyl‐3‐(2‐nitro‐5‐substitutedphenyl)‐4,5‐dihydro‐1H‐pyrazoles, and 19 1‐acyl‐3‐(2‐amino‐5‐substituted)‐4,5‐dihydro‐1H‐pyrazoles, were completely assigned using the concerted application of one‐ and two‐dimensional NMR experiments (DEPT, gs‐HSQC and gs‐HMBC). Copyright © 2012 John Wiley & Sons, Ltd.
Elucidating ‘undecipherable’ chemical structures using computer‐assisted structure elucidation approaches
Authors: Elyashberg Mikhail , Blinov Kirill , Molodtsov Sergey , Williams Antony
Published: January 2012

Structure elucidation using 2D NMR data and application of traditional methods of structure elucidation are known to fail for certain problems. In this work, it is shown that computer‐assisted structure elucidation methods are capable of solving such problems. We conclude that it is now impossible to evaluate the capabilities of novel NMR experimental techniques in isolation from expert systems developed for processing fuzzy, incomplete and contradictory information obtained from 2D NMR spectra. Copyright © 2012 John Wiley & Sons, Ltd.
The importance of supervision in retention of CNAs
Authors: Choi JiSun , Johantgen Meg
Published: January 2012

Certified nursing assistants (CNAs) provide the majority of direct care in nursing homes, yet recruiting and retaining CNAs has been difficult. Retaining CNAs is important because it has been linked to the better quality of resident care in nursing homes. In this study, the investigators examined the relationships of work‐related and personal factors to CNA job satisfaction and intent to leave. Linked data from the 2004 National Nursing Home Survey and the 2004 National Nursing Assistant Survey were analyzed using multilevel logistic regression. Personal factors such as age, education, and job history, were related to intent to leave but not to job satisfaction. Supportive supervision was a significant predictor of both job satisfaction and intent to leave. © 2012 Wiley Periodicals, Inc. Res Nurs Health 35:187–199, 2012
PAI‐1 promotes the accumulation of exudate macrophages and worsens pulmonary fibrosis following type II alveolar epithelial cell injury
Authors: Osterholzer John J , Christensen Paul J , Lama Vibha , Horowitz Jeffrey C , Hattori Noboru , Subbotina Natalya , Cunningham Andrew , Lin Yujing , Murdock Benjamin J , Morey Roger E , Olszewski Michal A , Lawrence Daniel A , Simon Richard H , Sisson Thomas H
Published: January 2012

Fibrotic disorders of the lung are associated with perturbations in the plasminogen activation system. Specifically, plasminogen activator inhibitor‐1 (PAI‐1) expression is increased relative to the plasminogen activators. A direct role for this imbalance in modulating the severity of lung scarring following injury has been substantiated in the bleomycin model of pulmonary fibrosis. However, it remains unclear whether derangements in the plasminogen activation system contribute more generally to the pathogenesis of lung fibrosis beyond bleomycin injury. To answer this question, we employed an alternative model of lung scarring, in which type II alveolar epithelial cells (AECs) are specifically injured by administering diphtheria toxin (DT) to mice genetically engineered to express the human DT receptor (DTR) off the surfactant protein C promoter. This targeted AEC injury results in the diffuse accumulation of interstitial collagen. In the present study, we found that this targeted type II cell insult also increases PAI‐1 expression in the alveolar compartment. We identified AECs and lung macrophages to be sources of PAI‐1 production. To determine whether this elevated PAI‐1 concentration was directly related to the severity of fibrosis, DTR+ mice were crossed into a PAI‐1‐deficient background (DTR+: PAI‐1−/−). DT administration to DTR+: PAI‐1−/− animals caused significantly less fibrosis than was measured in DTR+ mice with intact PAI‐1 production. PAI‐1 deficiency also abrogated the accumulation of CD11b+ exudate macrophages that were found to express PAI‐1 and type‐1 collagen. These observations substantiate the critical function of PAI‐1 in pulmonary fibrosis pathogenesis and provide new insight into a potential mechanism by which this pro‐fibrotic molecule influences collagen accumulation. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The organizational structure and governing principles of the Food and Drug Administration's Mini‐Sentinel pilot program
Authors: Forrow Susan , Campion Daniel M. , Herrinton Lisa J. , Nair Vinit P. , Robb Melissa A. , Wilson Marcus , Platt Richard
Published: January 2012

The US Food and Drug Administration's Mini‐Sentinel pilot program is developing an organizational structure as well as principles and policies to govern its operations. These will inform the structure and function of the eventual Sentinel System. Mini‐Sentinel is a collaboration that includes 25 participating institutions. We describe the program's current organizational structure and its major principles and policies. The organization includes a coordinating center with program leadership provided by a principal investigator; a planning board and subcommittees; an operations center; and data, methods, and protocol cores. Ad hoc workgroups are created as needed. A privacy panel advises about protection of individual health information. Principles and policies are intended to ensure that Mini‐Sentinel conforms to the principles of fair information practices, protects the privacy of individual health information, maintains the security and integrity of data, assures the confidentiality of proprietary information, provides accurate and timely communications, prevents or manages conflicts of interest, and preserves respect for intellectual property rights. Copyright © 2012 John Wiley & Sons, Ltd.
A systematic review of validated methods for identifying heart failure using administrative data
Authors: Saczynski Jane S. , Andrade Susan E. , Harrold Leslie R. , Tjia Jennifer , Cutrona Sarah L. , Dodd Katherine S. , Goldberg Robert J. , Gurwitz Jerry H.
Published: January 2012

Purpose

To identify and describe the validity of algorithms used to detect heart failure (HF) using administrative and claims data sources.

Methods

A systematic review of PubMed and Iowa Drug Information Service searches of the English language was performed to identify studies published between 1990 and 2010 that evaluated the validity of algorithms for the identification of patients with HF using and claims data. Abstracts and articles were reviewed by two study investigators to determine their relevance on the basis of predetermined criteria.

Results

The initial search strategy identified 887 abstracts. Of these, 499 full articles were reviewed and 35 studies included data to evaluate the validity of identifying patients with HF. Positive predictive values (PPVs) were in the acceptable to high range, with most being very high (>90%). Studies that included patients with a primary hospital discharge diagnosis of International Classification of Diseases, Ninth Revision, code 428.X had the highest PPV and specificity for HF. PPVs for this algorithm ranged from 84% to 100%. This algorithm, however, may compromise sensitivity because many HF patients are managed on an outpatient basis. The most common ‘gold standard’ for the validation of HF was the Framingham Heart Study criteria.

Conclusions

The algorithms and definitions used to identify HF using administrative and claims data perform well, particularly when using a primary hospital discharge diagnosis. Attention should be paid to whether patients who are managed on an outpatient basis are included in the study sample. Including outpatient codes in the described algorithms would increase the sensitivity for identifying new cases of HF. Copyright © 2012 John Wiley & Sons, Ltd.
Mini‐Sentinel's systematic reviews of validated methods for identifying health outcomes using administrative data: summary of findings and suggestions for future research
Authors: Carnahan Ryan M.
Published: January 2012

Purpose

The validity of findings from surveillance activities, which use administrative and claims data to link exposures to adverse events, depends in part on the validity of algorithms to identify health outcomes using these data. This review provides a high level overview of the findings of 19 systematic reviews of studies, which have examined the validity of algorithms to identify health outcomes using these data. The author categorized outcomes on the basis of the strength of evidence supporting valid algorithms to identify acute or incident events and suggested priorities for future validation studies.

Methods

The 19 reviews were evaluated, and key findings and suggestions for future research were summarized by a single reviewer. Outcomes with algorithms that consistently identified acute events or incident conditions with positive predictive values of greater than 70% across multiple studies and populations are described as low priority for future algorithm validation studies.

Results

Algorithms to identify cerebrovascular accidents, transient ischemic attacks, congestive heart failure, deep vein thrombosis, pulmonary embolism, angioedema, and total hip arthroplasty revision performed well across multiple studies and are considered low priority for future validation studies. Other outcomes were generally thought to require additional validation studies or algorithm refinement to be confident in algorithms. Few studies examined the validity of International Classification of Diseases, 10th Revision, codes.

Conclusion

Users of these reviews need to consider the generalizability of findings to their study populations. For some outcomes with poorly performing codes, it may always be necessary to validate cases. Copyright © 2012 John Wiley & Sons, Ltd.
A systematic review of validated methods for identifying transfusion‐related ABO incompatibility reactions using administrative and claims data
Authors: Carnahan Ryan M. , Kee Vicki R.
Published: January 2012

Purpose

This paper aimed to systematically review algorithms to identify transfusion‐related ABO incompatibility reactions in administrative data, with a focus on studies that have examined the validity of the algorithms.

Methods

A literature search was conducted using PubMed, Iowa Drug Information Service database, and Embase. A Google Scholar search was also conducted because of the difficulty identifying relevant studies. Reviews were conducted by two investigators to identify studies using data sources from the USA or Canada because these data sources were most likely to reflect the coding practices of Mini‐Sentinel data sources.

Results

One study was found that validated International Classification of Diseases (ICD‐9‐CM) codes representing transfusion reactions. None of these cases were ABO incompatibility reactions. Several studies consistently used ICD‐9‐CM code 999.6, which represents ABO incompatibility reactions, and a technical report identified the ICD‐10 code for these reactions. One study included the E‐code E8760 for mismatched blood in transfusion in the algorithm. Another study reported finding no ABO incompatibility reaction codes in the Healthcare Cost and Utilization Project Nationwide Inpatient Sample database, which contains data of 2.23 million patients who received transfusions, raising questions about the sensitivity of administrative data for identifying such reactions. Two studies reported perfect specificity, with sensitivity ranging from 21% to 83%, for the code identifying allogeneic red blood cell transfusions in hospitalized patients.

Conclusions

There is no information to assess the validity of algorithms to identify transfusion‐related ABO incompatibility reactions. Further information on the validity of algorithms to identify transfusions would also be useful. Copyright © 2012 John Wiley & Sons, Ltd.
A systematic review of validated methods for identifying anaphylaxis, including anaphylactic shock and angioneurotic edema, using administrative and claims data
Authors: Schneider Gary , Kachroo Sumesh , Jones Natalie , Crean Sheila , Rotella Philip , Avetisyan Ruzan , Reynolds Matthew W.
Published: January 2012

Purpose

The Food and Drug Administration's Mini‐Sentinel pilot program initially aims to conduct active surveillance to refine safety signals that emerge for marketed medical products. A key facet of this surveillance is to develop and understand the validity of algorithms for identifying health outcomes of interest from administrative and claims data. This article summarizes the process and findings of the algorithm review of anaphylaxis.

Methods

PubMed and Iowa Drug Information Service searches were conducted to identify citations applicable to the anaphylaxis health outcome of interest. Level 1 abstract reviews and Level 2 full‐text reviews were conducted to find articles using administrative and claims data to identify anaphylaxis and including validation estimates of the coding algorithms.

Results

Our search revealed limited literature focusing on anaphylaxis that provided administrative and claims data–based algorithms and validation estimates. Only four studies identified via literature searches provided validated algorithms; however, two additional studies were identified by Mini‐Sentinel collaborators and were incorporated. The International Classification of Diseases, Ninth Revision, codes varied, as did the positive predictive value, depending on the cohort characteristics and the specific codes used to identify anaphylaxis.

Conclusions

Research needs to be conducted on designing validation studies to test anaphylaxis algorithms and estimating their predictive power, sensitivity, and specificity. Copyright © 2012 John Wiley & Sons, Ltd.
A systematic review of validated methods for identifying erythema multiforme major/minor/not otherwise specified, Stevens–Johnson Syndrome, or toxic epidermal necrolysis using administrative and claims data
Authors: Schneider Gary , Kachroo Sumesh , Jones Natalie , Crean Sheila , Rotella Philip , Avetisyan Ruzan , Reynolds Matthew W.
Published: January 2012

Purpose

The Food and Drug Administration's (FDA) Mini‐Sentinel pilot program aims to conduct active surveillance to refine safety signals that emerge for marketed medical products. A key facet of this surveillance is to develop and understand the validity of algorithms for identifying health outcomes of interest (HOIs) from administrative and claims data. This paper summarizes the process and findings of the algorithm review of erythema multiforme and related conditions.

Methods

PubMed and Iowa Drug Information Service searches were conducted to identify citations applicable to the erythema multiforme HOI. Level 1 abstract reviews and Level 2 full‐text reviews were conducted to find articles that used administrative and claims data to identify erythema multiforme, Stevens–Johnson syndrome, or toxic epidermal necrolysis and that included validation estimates of the coding algorithms.

Results

Our search revealed limited literature focusing on erythema multiforme and related conditions that provided administrative and claims data‐based algorithms and validation estimates. Only four studies provided validated algorithms and all studies used the same International Classification of Diseases code, 695.1. Approximately half of cases subjected to expert review were consistent with erythema multiforme and related conditions.

Conclusions

Updated research needs to be conducted on designing validation studies that test algorithms for erythema multiforme and related conditions and that take into account recent changes in the diagnostic coding of these diseases. Copyright © 2012 John Wiley & Sons, Ltd.