bluuebunny/crossref_metadata_2025 huggingface dataset:
Ex vivo expansion of adipose tissue‐derived stem cells in spinner flasks
Authors: Zhu Yanxia , Liu Tianqing , Song Kedong , Fan Xiubo , Ma Xuehu , Cui Zhanfeng
Published: April 2009

Recent reports indicate that adipose tissue is a novel source of multipotent stem cells that can be used in cell therapy and tissue engineering. However, using the traditional cultivation of adipose tissue‐derived stem cells (ADSCs), it is hard to meet the needs of clinical applications. To obtain a large number of ADSCs while retaining their stemness, we seeded ADSCs in collagen/chitosan scaffolds and compared the proliferation of ADSCs in a 3‐D static environment in dishes and a 3‐D dynamic environment in spinner flask. The growth dynamic parameters of ADSCs were examined using a CCK‐8 kit every other day, and the variations of glucose and lactic acid concentrations were analyzed every day. After 14 days, the cells were observed under a scanning electron microscope. The surface markers (CD29, CD34, CD44, CD45, CD73, CD105, CD166 and HLA‐DR), the specific transcription factors (Nanog, Oct‐4, Sox‐2 and Rex‐1) and the multi‐differentiation potential (adipogenic, osteogenic and chondrogenic) were also assayed to identify the stemness of expanded cells. The results showed that the cells in scaffolds in spinner flask could be expanded by more than 26 times, and they presented better morphology and vitality and stronger differentiation ability than the cells cultivated in scaffolds statically. All the cells maintained stem cell characteristics after proliferation. Therefore, spinner flask cultivation is an easy‐to‐use, inexpensive system for expanding ADSCs in 3‐D scaffolds.
Simultaneous determination of five coumarins in Angelicae dahuricae Radix by HPLC/UV and LC‐ESI‐MS/MS
Authors: Park Ah Yeon , Park So‐Young , Lee Jaehyun , Jung Mihye , Kim Jinwoong , Kang Sam Sik , Youm Jeong‐Rok , Han Sang Beom
Published: April 2009

Rapid, simple and reliable HPLC/UV and LC‐ESI‐MS/MS methods for the simultaneous determination of five active coumarins of Angelicae dahuricae Radix, byakangelicol (1), oxypeucedanin (2), imperatorin (3), phellopterin (4) and isoimperatorin (5) were developed and validated. The separation condition for HPLC/UV was optimized using a Develosil RPAQUEOUS C30 column using 70% acetonitrile in water as the mobile phase. This HPLC/UV method was successful for providing the baseline separation of the five coumarins with no interfering peaks detected in the 70% ethanol extract of Angelicae dahuricae Radix. The specific determination of the five coumarins was also accomplished by a triple quadrupole tandem mass spectrometer equipped with an electrospray ionization source (LC‐ESI‐MS/MS). Multiple reaction monitoring (MRM) in the positive mode was used to enhance the selectivity of detection. The LC‐ESI‐MS/MS methods were successfully applied for the determination of the five major coumarins in Angelicae dahuricae Radix. These HPLC/UV and LC‐ESI‐MS/MS methods were validated in terms of recovery, linearity, accuracy and precision (intra‐ and inter‐day validation). Taken together, the shorter analysis time involved makes these HPLC/UV and LC‐ESI‐MS/MS methods valuable for the commercial quality control of Angelicae dahuricae Radix extracts and its pharmaceutical preparations. Copyright © 2009 John Wiley & Sons, Ltd.
Bioanalytical assay validation parameters re‐visited: perspectives on stability studies
Authors: Srinivas Nuggehally R.
Published: April 2009

Bioanalytical assay validation for plethora of parameters is considered vital for the reliable and accurate generation of raw analytical data used for pharmacokinetic characterization of analytes. Although the validation parameters have been widely accepted, the intent of this communication is to provide some perspectives on the commonly followed approaches for stability studies (i.e. freeze–thaw and long‐term freezer stability studies). The proposed discussion is intended to stimulate the thinking process to cut down on the extra work and/or maximize the efficiency in the bioanalytical work. Additionally, the availability of new emerging technological know‐hows and latest nuances in the field should provide the necessary impetus to innovate and articulate strategies for smart assay development/validation work for analytes. Copyright © 2009 John Wiley & Sons, Ltd.
Establishment of liquid chromatography/mass spectrometry for determination of bicyclol in rat single‐pass intestinal perfusion
Authors: Tan Wei , Wang Bao‐Lian , Hu Jin‐Ping , Sheng Li , Li Yan
Published: April 2009

A simple, rapid and sensitive method was developed for determination of bicyclol, a new synthetic anti‐hepatitis drug, in rat plasma from the mesenteric vein using a high‐performance liquid chromatography system coupled to a positive ion electrospray–mass spectrometric analysis. Bicyclol and internal standard (biphenyldicarboxylate, DDB) were isolated from plasma by liquid–liquid extraction, then separated on a Zorbax SB‐C18 column (3.5 µm, 2.1 × 100 mm) with mobile phase of methanol–water (60:40, v/v) at a flow rate of 0.2 mL/min. Detection was performed on a Trap XCT mass spectrometer equipped with an electrospray ionization (ESI) source operated in selected ion monitoring mode. Positive ion ESI was used to form sodium adduct molecular ions at m/z 413 for bicyclol and m/z 441 for DDB, respectively. A linear detection response was obtained for bicyclol ranging from 3.3 to 333.3 ng/mL and the lower limit of quantitation was 3.3 ng/mL. The coefficients of variation for intra‐ and inter‐day precisions were 1.1–7.7 and 2.0–6.6%, respectively. The percentage of absolute recovery of bicyclol was 85.3–94.6%. All analytes proved to be stable during all sample storage, preparation and analytic procedures. The method was successfully applied to determine the plasma concentration of bicyclol in mesenteric vein after intestinal perfusion. Copyright © 2009 John Wiley & Sons, Ltd.
Assay of free captopril in human plasma as monobromobimane derivative, using RPLC/(+)ESI/MS/MS: validation aspects and bioequivalence evaluation
Authors: Medvedovici Andrei , Albu Florin , Sora Iuliana Daniela , Udrescu Stefan , Galaon Toma , David Victor
Published: April 2009

A sensitive method for determination of free captopril as monobromobimane derivative in plasma samples is discussed. The internal standard (IS) was 5‐methoxy‐1H‐benzimidazole‐2‐thiol. Derivatization with monobromobimane immediately after blood collection and plasma preparation prevents oxidation of captopril to the corresponding disulfide compound and enhances the ionization yield. Consequently, derivatization enhances sample stability and detection sensitivity. Addition of the internal standard was made immediately after plasma preparation. The internal standard was also derivatized by monobromobimane, as it contains a thiol functional group. Preparation of plasma samples containing captopril and IS derivatives was based upon protein precipitation through addition of acetonitrile, in a volumetric ratio 1:2. The reversed‐phase liquid chromatographic separation was achieved on a rapid resolution cartridge Zorbax SB‐C18, monitored through positive electrospray ionization and tandem MS detection using the multiple‐reaction monitoring mode. Transitions were 408–362 amu for the captopril derivative and 371–260 amu for the internal standard derivative. The kinetics of captopril oxidation to the corresponding disulfide compound in plasma matrix was also studied using the proposed method. A linear log–log calibration was obtained over the concentration interval 2.5–750 ng/mL. A low limit of quantitation in the 2.5 ng/mL range was obtained. The analytical method was fully validated and successfully applied in a three‐way, three‐period, single‐dose (50 mg), block‐randomized bioequivalence study for two pharmaceutical formulations (captopril LPH 25 and 50 mg) against the comparator Capoten 50 mg. Copyright © 2009 John Wiley & Sons, Ltd.
Effects of false‐evidence ploys and expert testimony on jurors' verdicts, recommended sentences, and perceptions of confession evidence
Authors: Woody William Douglas , Forrest Krista D.
Published: April 2009

During interrogations, police may use false‐evidence ploys or fabricated claims to convince suspects to confess. Mock jurors read trial materials containing interrogation transcripts with or without a false‐evidence ploy and one of two expert witness conditions (present or absent). We examined jurors' verdicts, recommended sentences, and perceptions of the interrogation. Although factual evidence and the defendant's confession remained constant across conditions, false‐evidence ploys led to fewer convictions and shorter sentences. Jurors also perceived interrogations with ploys as more deceptive and coercive. Expert testimony reduced convictions and increased interrogation deception and coercion ratings. Across ploy types, participants rated demeanor ploys as less deceptive and recommended longer sentences for confessors. Outcomes reveal important, previously unrecognized consequences of false‐evidence ploys. Copyright © 2009 John Wiley & Sons, Ltd.
Chemical networks with inflows and outflows: A positive linear differential inclusions approach
Authors: Angeli David , De Leenheer Patrick , Sontag Eduardo D.
Published: April 2009

Certain mass‐action kinetics models of biochemical reaction networks, although described by nonlinear differential equations, may be partially viewed as state‐dependent linear time‐varying systems, which in turn may be modeled by convex compact valued positive linear differential inclusions. A result is provided on asymptotic stability of such inclusions, and applied to a ubiquitous biochemical reaction network with inflows and outflows, known as the futile cycle. We also provide a characterization of exponential stability of general homogeneous switched systems which is not only of interest in itself, but also plays a role in the analysis of the futile cycle. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Susceptibility of mouse minute virus to inactivation by heat in two cell culture media types
Authors: Schleh Marc , Romanowski Peter , Bhebe Prince , Zhang Li , Chinniah Shivanthi , Lawrence Bill , Bashiri Houman , Gaduh Asri , Rajurs Viveka , Rasmussen Brian , Chuck Alice , Dehghani Houman
Published: April 2009

Viral contaminations of biopharmaceutical manufacturing cell culture facilities are a significant threat and one for which having a risk mitigation strategy is highly desirable. High temperature, short time (HTST) mammalian cell media treatment may potentially safeguard manufacturing facilities from such contaminations. HTST is thought to inactivate virions by denaturing proteins of the viral capsid, and there is evidence that HTST provides ample virucidal efficacy against nonenveloped or naked viruses such as mouse minute virus (MMV), a parvovirus. The aim of the studies presented herein was to further delineate the susceptibility of MMV, known to have contaminated mammalian cell manufacturing facilities, to heat by exposing virus‐spiked cell culture media to a broad range of temperatures and for various times of exposure. The results of these studies show that HTST is capable of inactivating MMV by three orders of magnitude or more. Thus, we believe that HTST is a useful technology for the purposes of providing a barrier to adventitious contamination of mammalian cell culture processes in the biopharmaceutical industry. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
The identification of enzyme targets for the optimization of a valine producing Corynebacterium glutamicum strain using a kinetic model
Authors: Magnus Jørgen Barsett , Oldiges Marco , Takors Ralf
Published: April 2009

The enzyme targets for the rational optimization of a Corynebacterium glutamicum strain constructed for valine production are identified by analyzing the control of flux in the valine/leucine pathway. The control analysis is based on measurements of the intracellular metabolite concentrations and on a kinetic model of the reactions in the investigated pathway. Data‐driven and model‐based methods are used and evaluated against each other. The approach taken gives a quantitative evaluation of the flux control and it is demonstrated how the understanding of flux control is used to reach specific recommendations for strain optimization. The flux control coefficients (FCCs) with respect to the valine excretion rate were calculated, and it was found that the control is distributed mainly between the acetohydroxyacid synthase enzyme (FCC = 0.32), the branched chain amino acid transaminase (FCC = 0.27), and the exporting translocase (FCC = 0.43). The availability of the precursor pyruvate has substantial influence on the valine flux, whereas the cometabolites are less important as demonstrated by the calculation of the respective response coefficients. The model is further used to make in‐silico predictions of the change in valine flux following a change in enzyme level. A doubling of the enzyme level of valine translocase will result in an increase in valine flux of 31%. By optimizing the enzyme levels with respect to valine flux it was found that the valine flux can be increased by a factor 2.5 when the optimal enzyme levels are implemented. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Characterization of pharmacogenetically relevantCYP2D6andABCB1gene polymorphisms in a Portuguese population sample
Authors: Correia C. , Santos P. , Coutinho A. M. , Vicente A. M.
Published: April 2009

Differences in metabolism of drugs can lead to severe toxicity or therapeutic failure. In addition to cytochrome P450 2D6, which plays a critical role in drug metabolism,ABCB1encoded P‐glycoprotein (PGP) is also an important determinant in drug bioavailability. The genes encoding these molecules are highly variable among populations and, given their clinical importance in drug therapy, determiningCYP2D6andABCB1allele frequencies in specific populations is very important for useful application in clinical settings. In this study the frequency of the pharmacologically relevantCYP2D6*3, *4, *5, *6 allelic variants and gene duplication, andABCB1C1236T and C3435T gene polymorphisms and their haplotypes was determined in a population sample of 100 Portuguese healthy subjects.CYP2D6allele frequencies were 1.4% (*3), 13.3% (*4), 2.8% (*5), 1.8% (*6) and 6.1% (gene duplication), with 5% of the individuals classified as PM and 8.4% as UM. The frequencies obtained for the non‐functional alleles and for theCYP2D6gene duplication are in agreement with other South European populations, and reinforce the previously suggested south/north gradient ofCYP2D6duplications. Allelic frequencies for theABCB1polymorphisms were 52% (3435C) and 54% (1236C) and the most common haplotype (1236C‐3435C) occurred with a frequency of 45.5%. Although allele and haplotype frequency data forABCB1in Southern Europe is limited, some discrepancies were found with other European populations, with possible therapeutic implications for PGP substrate drugs. Copyright © 2009 John Wiley & Sons, Ltd.
Probing the Role of Backbone Hydrogen Bonding in a Critical β Sheet of the Extracellular Domain of a Cys‐Loop Receptor
Authors: Gleitsman Kristin R. , Lester Henry A. , Dougherty Dennis A.
Published: April 2009

Probing the sheet: The network of hydrogen bonds formed in the outer β sheet of the nicotinic acetylcholine receptor (nAChR; see figure) is fairly robust and tolerates single amide‐to‐ester mutations throughout. However, eliminating two proximal hydrogen bonds completely destroys receptor function; this adds further support to gating models that ascribe important roles to these β strands of the nAChR extracellular domain.

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Long‐range communication is essential for the function of members of the Cys‐loop family of neurotransmitter‐gated ion channels. The involvement of the peptide backbone in binding‐induced conformational changes that lead to channel gating in these membrane proteins is an interesting, but unresolved issue. To probe the role of the peptide backbone, we incorporated a series of α‐hydroxy acid analogues into the β‐sheet‐rich extracellular domain of the muscle subtype of the nicotinic acetylcholine receptor, the prototypical Cys‐loop receptor. Specifically, mutations were made in β strands 7 and 10 of the α subunit. A number of single backbone mutations in this region were well tolerated. However, simultaneous introduction of two proximal backbone mutations led to surface‐expressed, nonfunctional receptors. Together, these data suggest that while the receptor is remarkably robust in its ability to tolerate single amide‐to‐ester mutations throughout these β strands, more substantial perturbations to this region have a profound effect on the protein. These results support a model in which backbone movements in the outer β sheet are important for receptor function.
Histone H3 N‐Terminal Peptide Binds Directly to Its Own mRNA: A Possible Mode of Feedback Inhibition to Control Translation
Authors: Lee Kyung Hyun , Lee Nam Ju , Hyun Soonsil , Park Yong Keun , Yang Eun Gyeong , Lee Jun‐Kyu , Jeong Sunjoo , Yu Jaehoon
Published: April 2009

Give me some feedback: In vitro selection of aptamers against the H3 peptide provided specific hairpin RNAs that possess high homology with histone H3 mRNA. The identified H3 hairpin RNA binds specifically to the H3 peptide with micromolar affinity and dose‐dependently inhibits in vitro translation of the H3 protein. Consequently, the hairpin RNA and H3 peptide are one of the rare cis‐ and trans‐elements on coding regions found among housekeeping proteins in higher eukaryotes.

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Numerical Simulation of the Hydrodynamics of Gas/Solid Two‐Phase Flow in a Circulating Fluidized Bed with Different Inlet Configurations
Authors: Li Y. , Ma B. , Hu J. , Zhao K.
Published: April 2009

The gas/solid flow characteristics in a circulating fluidized bed with two different inlet configurations were investigated by numerical simulation based on an Eulerian approach. In order to describe the interaction between the gas phase and the solid phase and the influence of the solid phase on the gas turbulence, a source term formulation with a more reasonable physical meaning was introduced. The simulation results were validated by the experimental data; then, the model was employed to examine the effect of the inlet configuration on the gas and solid feeding. The simulation results showed that, using the side feeding system, the distributions of solid flow and concentration were highly variable both over the column cross‐section and along the column height. However, such variations can be improved by using the elbow inlet system where the gas and solid are fed from the bottom.
Interaction Parameter Method for Investigating BTEX Extraction Using the Hollow‐Fiber Microporous Membrane Liquid/Liquid Extraction Technique
Authors: Liu Y. , Shi B.
Published: April 2009

This work focused on the extraction of BTEX from aqueous solution by a hollow‐fiber microporous membrane liquid/liquid extraction (HF‐MMLLE) technique. A simple and rapid method based on the Hansen solubility parameters (HSP) theory was adopted to theoretically determine the interaction parameter (χ12) between the extractants and BTEX. Experiments were carried out to establish the relationship between the interaction parameter and the extraction performance. Furthermore, the distribution coefficient and permeability coefficient related to the extraction performance were also discussed, which verified the relationship from a quantitative idea. It was observed that the liquid/liquid extraction was based on the strong affinities between the extractants and the target pollutants. This method should be paid more attention for its potential application in other solvent‐sensitive processes.
Gas‐Liquid Mass Transfer in Fibrous Bed Reactor with Counter‐Current Liquid Recycle
Authors: Martinov M. , Hadjiev D. , Vlaev S. D.
Published: April 2009

In this work, the gas‐liquid mass transfer in a lab‐scale fibrous bed reactor with liquid recycle was studied. The volumetric gas‐liquid mass transfer coefficient, kLa, is determined over a range of the superficial liquid velocity (0.0042–0.0126 m.s–1), gas velocity (0.006–0.021 m.s–1), surface tension (35–72 mN/m), and viscosity (1–6 mPa.s). Increasing fluid velocities and viscosity, and decreasing interfacial tension, the volumetric oxygen transfer coefficient increased. In contrast to the case of co‐current flow, the effect of gas superficial velocity was found to be more significant than the liquid superficial velocity. This behavior is explained by variation of the coalescing gas fraction and the reduction in bubble size. A correlation for kLa is proposed. The predicted values deviate within ± 15 % from the experimental values, thus, implying that the equation can be used to predict gas‐liquid mass transfer rates in fibrous bed recycle bioreactors.
Heat Transfer and Friction Characteristics for Turbulent Flow of Dimpled Tubes
Authors: Wang Y. , He Y.‐L. , Li R. , Lei Y.‐G.
Published: April 2009

The hydrodynamic and heat transfer characteristics of dimpled tubes with different arrangements were investigated in this paper. The dimples on the tube are outward‐facing, raised, with aligned and staggered arrangements. The experiments were carried out in counter‐current flow patterns with cold air along the tube inside and hot water around the outside of the tube. The Reynolds numbers of air flow were in the range of 1.6·104to 5.4·104. By comparing the performances among three tubes (smooth tube, dimpled tube with aligned arrangement, and dimpled tube with staggered arrangement), we could find that the dimpled tubes enhanced the Nusselt number by about 18.6∼22.7 %, while the friction factors of the dimpled tubes increased by 18.6∼25.9 % for the aligned arrangement and by 14.3∼29.8 % for the staggered arrangement. The test results also showed that different dimple arrangements have very little effect, which is always within 5 %. By the integrated performance evaluation of (Nua/Nus)/(fa/fs)1/3, the maximum of the heat transfer enhancement with the same friction penalty, about 19 %, could be achieved by optimization of the dimpled‐tube design.
Important Parameters of Epoxidation of 1,4‐bis(allyloxy)butane in Aqueous‐Organic Phase Transfer Catalytic System
Authors: Kaczmarczyk E. , Milchert E. , Janus E.
Published: April 2009

The epoxidation of 1,4‐bis(allyloxy)butane to give 1‐allyloxy‐4‐glycidoloxybutane and 1,4‐bis(glycidoloxy)butane was investigated. The reaction was carried out with 30 wt % hydrogen peroxide under phase transfer catalysis (PTC) conditions in the presence of sodium tungstate(VI) dihydrate and orthophosphoric(V) acid (WO42–/PO43–). Methyltrioctylammonium chloride (Aliquat 336) was used as the phase transfer catalyst. The effect of agitation speed and reaction temperature on the yield of epoxidation products was determined.
Cage Chirality of PC Cage Compounds: Highly Diastereoselective Formation of Diastereomeric P5‐Deltacyclenes, Separation of Diastereomers, and Removal of the Chiral Auxiliary
Authors: Hofmann Martin , Höhn Christine , Heinemann Frank W. , Zenneck Ulrich
Published: April 2009

Cage chirality: Cyclic addition reactions of chirally modified stannyl‐1,2,4‐triphospholes with tBuCP leads to stannylated P5‐deltacyclenes in high yields as separable 1:1 mixtures of diastereomers. Destannylation of a separated diastereomer gives a single enantiomer of an optically pure PC cage compound. The novel cage‐chiral P5C4 unit (shown here) dominates the chiroptical properties, not only of the isolated enantiomer, but of the diastereomeric compounds as well.

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An effective cyclic addition reaction of diastereomeric (R*)diphenyltin‐3,5‐di(tert‐butyl)‐1,2,4‐triphosphole derivatives 6 a–c (R*=(−)‐cis‐myrtanyl (a), (−)‐trans‐myrtanyl (b), m‐(2‐bornyl‐2‐ene)phenyl (c) with two equivalents of tert‐butylphosphaalkyne 1 leads to 1:1 mixtures of diastereomeric stannylated pentaphosphadeltacyclene derivatives 7 a–c with seven stereogenic centers in the cage unit. The (−)‐cis‐myrtanyl derivative 7 a could be separated into its diastereomers; destannylation of diastereomer 7 a(RR) led to the PH cage 8 as a pure enantiomer. Circular dichroism (CD) spectroscopy of the pure diastereomer 7 a(RR) and the enantiomer 8 give evidence for identical stereoisomers of the P5‐deltacyclene cage units and prove a strong dominance of the chiral cages over the chiral auxiliary groups with respect to their chiroptical properties. Absolute X‐ray structure investigations of the majority of the compounds presented in the paper reveal the details of the stereochemistry of the asymmetric PC cage units. In this paper we demonstrated for the first time a general preparative route to stereochemically fully defined asymmetric PC cage compounds by separation of diastereomers and replacement of the chiral auxiliary group.
Predicting the NMR Spectra of Paramagnetic Molecules by DFT: Application to Organic Free Radicals and Transition‐Metal Complexes
Authors: Rastrelli Federico , Bagno Alessandro
Published: April 2009

Nuclear shieldings, including the Fermi contact and pseudocontact terms, have been calculated with DFT methods in a variety of open‐shell molecules (nitroxides, aryloxyl and various transition‐metal complexes), thereby predicting 1H and 13C chemical shifts. In general, when experimental data are reliable a good agreement with experimental values is observed, thus demonstrating the predictive power of DFT also in this context. However, the general accuracy is lower than that for closed‐shell species. A few inconsistencies in literature values are reconciled by reassigning some shifts. Structural, magnetic, and dynamic parameters have also been put into the Solomon–Bloembergen equations to predict signal line shapes, in particular those of signals that are difficult to locate or are undetectable. Guidelines are provided to predict the order of magnitude of relaxation rates. It is shown that DFT‐predicted paramagnetic shifts can greatly assist in obtaining and understanding the NMR spectra of paramagnetic molecules, which generally require different experimental strategies and exhibit problems in detection and assignment.
Quenching Mechanisms and Diffusional Pathways in Micellar Systems Unravelled by Time‐Resolved Magnetic‐Field Effects
Authors: Goez Martin , Henbest Kevin B. , Windham Emma G. , Maeda Kiminori , Timmel Christiane R.
Published: April 2009

Radical observation: Time‐resolved magnetic‐field effects yield a very detailed picture of electron‐transfer quenching in micelles and of the fate of the resulting radical‐ion pairs. The system xanthone/DABCO (A/D, see figure) permits a separation of the different static and dynamic quenching pathways and a distinction between bulk and surface diffusion.

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Magnetic‐field effects (MFEs) are used to investigate the photoreaction of xanthone (A) and DABCO (D) in anionic (SDS) or cationic (DTAC) micelles at high pH (DABCO=1,4‐diazabicyclo[2.2.2]octane, SDS=sodium dodecyl sulfate, DTAC=dodecyl trimethyl ammonium chloride). From MFE experiments with nanosecond time resolution, the radical anion A.− can be observed without any interference from the much more strongly absorbing triplet 3A*, the different quenching processes can be separated and their rates can be measured. Triplet 3A* is quenched dynamically both by the SDS micelle (k1=5.0×105 s−1) and by DABCO approaching from the aqueous phase (k2=2.0×109 M−1 s−1). Static quenching by solubilised DABCO (association constant with the SDS micelles, 1.5 M−1) also participates at high DABCO concentrations, but is chemically nonproductive and does not lead to MFE generation. The MFEs stemming from the radical ion pairs ${\overline {{\rm{A}}^{ \bullet - } \,{\rm{D}}^{ \bullet + } } }$ are about 40 times larger in the anionic micelles than in the cationic ones despite a higher yield of free radicals in the latter case. This can be rationalised by different diffusional dynamics: Because of the location of their precursors, A.− and D.+ are formed at opposite sides of the micelle boundary. Subsequently, the negatively charged Stern layer of the SDS micelle traps the radical cation, which then undergoes surface diffusion, so both the recombination probability and the spin mixing are high; in contrast, the positive surface charge of the DTAC micelle forces the radical cation into the bulk of the solution, thus efficiently blocking a recombination.
Highly Enantio‐ and Diastereoselective Organocatalytic Desymmetrization of Prochiral Cyclohexanones by Simple Direct Aldol Reaction Catalyzed by Proline
Authors: Companyó Xavier , Valero Guillem , Crovetto Luis , Moyano Albert , Rios Ramon
Published: April 2009

Panacea for aldol desymmetrizations: We describe an easy entry for the desymmetrization of 4‐substituted‐cyclohexanones catalyzed by proline, using as cocatalysts different hydrogen‐bonding donors (see scheme), which dramatically improves the catalytic efficiency of proline in desymmetrization reactions.

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Conform or rebel: when does keeping to the rules enhance firm performance?
Authors: Eapen Alex , Krishnan Rekha
Published: April 2009

This paper examines whether there are economic rewards to mimicking strategic actions of other firms. The strategic behaviour we study is the formation of technology collaborations with MNEs by Indian firms. We argue that conforming to the behaviour of other firms has differential performance effects across different classes of firms and suggest that the benefits of conformity accrue more to small than large firms. To test this, we measured each Indian firm's conformity to the average tendency of other similar firms to collaborate with an MNE and then regressed its performance on conformity. Results were consistent with our expectations that small firms gain more from conformity than do their larger counterparts. Copyright © 2009 ASAC. Published by John Wiley & Sons, Ltd.
The β‐thymosins: Intracellular and extracellular activities of a versatile actin binding protein family
Authors: Mannherz Hans Georg , Hannappel Ewald
Published: April 2009

The β‐thymosins are N‐terminally acetylated peptides of about 5 kDa molecular mass and composed of about 40–44 amino acid residues. The first member of the family, thymosin β4, was initially isolated from thymosin fraction 5, prepared in five steps from calf thymus. Thymosin β4 was supposed to be specifically produced and released by the thymic gland and to possess hormonal activities modulating the immune response. Various paracrine effects have indeed been reported for these peptides such as cardiac protection, angiogenesis, stimulation of wound healing, and hair growth. Besides these paracrine effects, it was noted that β‐thymosins occur in high concentration in the cytoplasm of many eukaryotic cells and bind to the cytoskeletal component actin. Subsequently it became apparent from in vitro experiments that they preferentially bind to monomeric (G‐)actin and stabilize it in its monomeric form. Due to this ability the β‐thymosins are the main intracellular actin sequestering factor, i.e., they posses the ability to remove monomeric actin from the dynamic assembly and disassembly processes of the actin cytoskeleton that constantly occur in activated cells. In this review we will concentrate on the intracellular activity and localization of the β‐thymosins, i.e., their modulating effect on the actin cytoskeleton. Cell Motil. Cytoskeleton, 2009. © 2009 Wiley‐Liss, Inc.
Further Evidence of the Anti‐inflammatory Effects of Silver Nanoparticles
Authors: Wong Kenneth K. Y. , Cheung Stephanie O. F. , Huang Liuming , Niu Jun , Tao Chang , Ho Chi‐Ming , Che Chi‐Ming , Tam Paul K. H.
Published: April 2009

The production of pure silverin nanoparticle size has opened new dimensions in the clinical use of this precious metal. We and others have demonstrated previously that silver nanoparticles (nAg) possess efficient antimicrobial activity. Herein we show they may also have significant anti‐inflammatory effects in a postoperative peritoneal adhesion model. This finding provides further insight into the biological actions of nAg as well as a potentially novel therapy for peritoneal adhesions in clinical surgery.

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With the advent of nanoscience, pure silver can now be made into nanometer‐sized particles. As a result, we are able to explore the potentially beneficial properties of pure silver. In our previous study using a burn wound model in mice, we demonstrated that besides antibacterial action, silver nanoparticles (nAg) appear to have anti‐inflammatory properties. Herein we further confirm the anti‐inflammatory effects of nAg and explore their potential clinical application through a postoperative peritoneal adhesion model. We also elucidate the potential mechanism of action of silver. Our in vitro and in vivo experimental findings show that nAg are effective at decreasing inflammation in peritoneal adhesions without significant toxic effects. This study thus provides further evidence for and contributes to the understanding of the anti‐inflammatory properties of nAg and may also give a novel therapeutic direction for the prevention of postoperative adhesions.
Discovery of a New Class of Non‐imidazole Oxazoline‐Based Histamine H3 Receptor (H3R) Inverse Agonists
Authors: Célanire Sylvain , Wijtmans Maikel , Christophe Bernard , Collart Philippe , de Esch Iwan , Dassesse Donald , Delaunoy Christel , Denonne Frédéric , Durieu Véronique , Gelens Edith , Gillard Michel , Lallemand Bénédicte , Lamberty Yves , Lebon Florence , Nicolas Jean‐Marie , Quéré Luc , Snip Erwin , Vanbellinghen Alain , Van houtvin Nathalie , Verbois Valérie , Timmerman Henk , Talaga Patrice , Leurs Rob , Provins Laurent
Published: April 2009

H3R inverse agonists based on an aminopropoxy‐phenyloxazoline framework constitute highly valuable druglike lead compounds that display efficacy in a mouse model of recognition memory.

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Conformational Landscape of Supersonically Expanded 1‐(Fluorophenyl)ethanols and Their Monohydrated Clusters
Authors: Speranza Maurizio , Rondino Flaminia , Giardini Anna , Paladini Alessandra , Hortal Ana R. , Piccirillo Susanna , Satta Mauro
Published: April 2009

The effects of the presence of the ring fluorine atom on the conformational landscape of supersonically expanded isomeric 1‐(fluorophenyl)ethanols and their monohydrated clusters are investigated by resonant two‐photon ionization (R2PI) spectroscopy, coupled with time‐of‐flight (TOF) mass spectrometry. In contrast to the very simple spectrum of 1‐phenylethanol, the lack of structural symmetry of the aromatic rings of isomeric 1‐(fluorophenyl)ethanols generates more complicated spectra, characterized by several low‐frequency progressions of bands. Their interpretation is based on the strict correspondence with theoretical predictions at the D‐B3LYP/6‐31G** level of theory. Monohydration of the 1‐(fluorophenyl)ethanol isomers favours exclusive formation of the corresponding conformers, characterized by the OH⋅⋅⋅OwH⋅⋅⋅π intracomplex interaction and whose excitation spectrum exhibits features attributed to the C1Cα torsion plus intermolecular water torsion.
Fluorescence activated cell sorting of live female germ cells and somatic cells of the mouse fetal gonad based on forward and side scattering
Authors: Wojtasz Lukasz , Daniel Katrin , Toth Attila
Published: April 2009

Analysis of female mammalian germ cells has been hindered by difficulties in isolating high purity germ cell populations from embryonic and fetal gonads. Meiotic prophase stage oocytes are particularly difficult to isolate due to the lack of suitable surface markers. Oct4 promoter driven GFP expression has been used to distinguish germ cells/oocytes (GFP positive) from somatic cells (GFP negative), however, the requirement for transgenic animals has limited the use of this technique. We analyzed the side‐ and forward scattering properties of living cell populations obtained from fetal ovaries of Oct4‐GFP transgenic and wild‐type mice. On the basis of these measurements, we defined criteria that allow the discrimination and identification of germ cells and somatic cells within cell suspensions of nontransgenic female fetal gonads. The described method is suitable for the isolation of populations of germ cells and somatic cells of higher than 90% purity. We also demonstrated that the sorted cells can be used in downstream immunofluorescence and RT‐PCR applications. Hence, we conclude that side and forward scattering based sorting of female germ cells is a valuable tool that will benefit the understanding of female gametogenesis. © 2009 International Society for Advancement of Cytometry
Security analysis of mCrypton proper to low‐cost ubiquitous computing devices and applications
Authors: Park Jong Hyuk
Published: April 2009

mCrypton, which is a mini‐version of Crypton, is a 64‐bit block cipher with three key size options (64 bits, 96 bits, 128 bits). It was designed for use in low‐cost ubiquitous wireless devices and resource‐constrained tiny devices such as low‐cost Radio‐Frequency Identification tags and sensors in Ubiquitous Sensor Network. In this paper we show that 8‐round mCrypton with 128‐bit key is vulnerable to related‐key rectangle attack. We first describe how to construct two related‐key truncated differentials on which 7‐round related‐key rectangle distinguisher is based and then we exploit it to attack 8‐round mCrypton. This attack requires 246 dada and 246 time complexities, which is faster than exhaustive search. This is the first known cryptanalytic result on mCrypton. Copyright © 2009 John Wiley & Sons, Ltd.
Mycobacterium avium complex infection in a neck abscess: A diagnostic pitfall in fine‐needle aspiration biopsy of head and neck lesions
Authors: Fitzhugh Valerie A. , McCash Samuel I. , Park Eunice , Wiesenthal Carl , LaBombardi Vincent , Chen Hua
Published: April 2009

Fine‐needle aspiration biopsy (FNAB) is a useful tool in the diagnosis of mycobacterial disease, especially Mycobacterium tuberculosis. However, nontuberculous mycobacterial infection diagnosed with FNAB material is much rarer, with Mycobacterium avium complex being the most common. In this report, we present the case of a 21‐year‐old HIV positive man, who presented with a unilateral, tender, enlarging cervical neck mass. FNAB had revealed acute inflammation. Mycobacterium avium complex grew in culture from the material that was aspirated and was confirmed by DNA probe. Because of the paucity of articles on this subject in the cytology literature, it is important to reiterate the value of the material aspirated at the bedside and the clinic in the diagnosis of infectious disease. When faced with antibiotic‐resistant cellulitis and abscesses, the FNAB material must be sent for acid fast bacteria smears and culture. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.
Utility of glypican‐3 and survivin in differentiating hepatocellular carcinoma from benign and preneoplastic hepatic lesions and metastatic carcinomas in liver fine‐needle aspiration biopsies
Authors: Nassar A. , Cohen C. , Siddiqui M. T.
Published: April 2009

Glypican‐3 (GPC‐3), a membrane‐anchored heparin sulfate proteoglycan, has been shown to be expressed in ∼80% of hepatocellular carcinoma (HCC) but not in benign hepatic lesions. Survivin, a novel inhibitor of apoptosis, and a prognostic marker, has also been expressed in HCC. We evaluated these two immunomarkers (GPC‐3 and survivin) in differentiating HCC from benign and preneoplastic hepatic lesions and metastatic carcinomas, comparing them to HepPar‐1 (hepatocyte paraffin‐1) in liver fine‐needle aspiration biopsies (FNAB).

Immunohistochemistry for GPC‐3, survivin and HepPar‐1 was performed on 92 FNAB including HCC, hepatic cirrhosis, focal nodular hyperplasia (FNH), hepatic adenoma, dysplastic hepatic nodules and metastatic carcinomas. Immunostaining was scored as positive, if ≥10% of tumor cells stained.

GPC‐3 is immunoexpressed in 56.8% of HCC, but not in benign and preneoplastic hepatic lesions, or metastatic carcinomas; whereas survivin is expressed in HCC (86.4%), benign hepatic lesions (85.7%), dysplastic hepatic nodules (100%) and metastatic carcinomas (94.3%). HepPar‐1 is immunoexpressed in HCC (72.7%), benign hepatic lesions (100%), dysplastic nodules (100%) and metastatic carcinomas (2.9%). The sensitivity and specificity of GPC‐3, survivin and HepPar‐1 for detection of HCC are 56.8 and 100%, 86.4 and 6.3%, 72.7 and 70.8%, respectively.

GPC‐3 is a reliable and more specific immunohistochemical marker than survivin for the diagnosis of HCC in FNAB. HepPar‐1, although a more sensitive marker than GPC‐3, has a lower specificity for detection of HCC. Our data supports the potentially significant diagnostic utility of GPC‐3 in FNABs in differentiating primary malignant from benign and preneoplastic liver lesions, and metastatic carcinomas. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.
Fine‐needle aspiration cytology in the diagnosis of malignant proliferating trichilemmal tumor: Report of a case and review of the literature
Authors: Kini Jyoti R. , Kini Hema
Published: April 2009

Malignant proliferating trichilemmal tumor is a rare cutaneous neoplasm derived from the outer root sheath of the hair follicle. Fine‐needle aspiration cytology is being increasingly used in the investigation of primary and metastatic cutaneous tumors. However, there are few reports on the cytology of trichilemmal tumors in the literature. We describe the cytological features of this uncommon adnexal tumor presenting as a scalp mass in a 58‐year‐old woman. In view of its aggressive biological behavior, it is crucial for cytologists to be aware of this rare lesion and distinguish it from primary cutaneous squamous‐cell carcinoma. The differences on fine‐needle aspiration cytology can be subtle and pose problems in diagnosis. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.
The anti‐interleukin‐1 in type 1 diabetes action trial—background and rationale
Authors: Pickersgill Linda M.S. , Mandrup‐Poulsen Thomas R.
Published: April 2009

Type 1 diabetes (T1D) is caused by an inflammatory destruction of pancreatic beta‐cells. Pro‐inflammatory cytokines, in particular interleukin‐1 (IL‐1), have been suggested to be effector molecules based on the observations that pro‐inflammatory cytokines cause beta‐cell apoptosis in vitro and aggravate diabetes in vivo, and that inhibition of the action of these cytokines reduce diabetes incidence in animal models of type 1 diabetes and islet graft destruction. This review presents the rationale for and design of a recently launched double‐blind, multicenter, randomized clinical trial that investigates the effect of interleukin‐1 antagonism on beta‐cell function in subjects with T1D of recent‐onset. Copyright © 2009 John Wiley & Sons, Ltd.
The prevalence of GAD antibodies in Korean women with gestational diabetes mellitus and their clinical characteristics during and after pregnancy
Authors: Yu Sung Hoon , Park Sunmin , Kim Hun‐Sung , Park So‐Young , Yim Chang Hoon , Han Ki Ok , Yoon Hyun Koo , Jang Hak Chul , Chung Ho Yeon , Kim Sung‐Hoon
Published: April 2009

Background

We conducted this research in order to evaluate the prevalence of glutamic acid decarboxylase antibodies (GADA) in Korean women with gestational diabetes mellitus (GDM), to identify the clinical characteristics of these women, and to gauge the prevalence of diabetes among them after childbirth.

Methods

We studied 887 Korean women with GDM who were screened for GADA, and assessed their antepartum clinical characteristics and the outcomes of their pregnancies. At 6 weeks' postpartum, 75 g oral glucose tolerance tests were performed to determine the diabetic status of GDM women with GADA.

Results

The prevalence of GADA in Korean women with GDM was 1.7%. Plasma glucose levels at 0‐ and 3‐h during oral glucose tolerance tests were significantly different between GADA‐positive and GADA‐negative women with GDM. There were no significant differences between them in terms of age, body mass index, family history of diabetes, fasting insulin, and lipid profiles. However, GADA‐positive women with GDM required insulin treatment during pregnancy more frequently than GADA‐negative patients. The development of diabetes at early postpartum was significantly higher in GADA‐positive women with GDM than those who were GADA negative.

Conclusions

The prevalence of GADA in Korean women with GDM was low. However, GADA‐positive women with GDM are more susceptible to subsequently developing type 1 diabetes, even in the early postpartum period. Long‐term follow up studies and intervention to prevent type 1 diabetes among GADA‐positive GDM women are needed. Copyright © 2009 John Wiley & Sons, Ltd.
Independent anti‐inflammatory effect of insulin in newly diagnosed type 2 diabetes
Authors: Mao Xiao‐Ming , Liu Hao , Tao Xiao‐Jun , Yin Guo‐Ping , Li Qian , Wang Shu‐Kui
Published: April 2009

Background

Although insulin has been reported to have an anti‐inflammatory effect, whether this effect is independent of its property to reduce blood glucose with insulin treatment in type 2 diabetes has not been investigated in detail. The purpose of this study was to evaluate the independent anti‐inflammatory effect of insulin in patients with newly diagnosed type 2 diabetes.

Research design and methods

An 8‐week, randomized, parallel‐group study that enrolled 90 patients with newly diagnosed type 2 diabetes, who were randomly assigned to receive either insulin or metformin, was carried out. The doses of insulin and metformin were titrated according to fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) during the 4 weeks; the target of FPG was 126 mg/dL and that of PPG was 160 mg/dL. The blood glucose levels were kept stabilized till the end of the study. The serum concentrations of high‐sensitive C‐reactive protein (hsCRP) and interleukin (IL)‐6 were measured before starting the study and 4 and 8 weeks after initiation of insulin or metformin therapy.

Results

After 4 weeks of dose titration, the levels of FPG were reduced in the two groups compared to baseline (p < 0.001), but there was no significant difference between the two groups (p > 0.05). During the next 4 weeks' treatment, the levels of FPG were stable, but the serum concentration of hsCRP and IL‐6 was markedly reduced in the insulin‐treated group compared with that in the metformin‐treated group (p < 0.001).

Conclusions

Our data suggest that insulin has an anti‐inflammatory effect that is independent of the reduction it causes in blood glucose. Copyright © 2009 John Wiley & Sons, Ltd.
Defensin‐related peptide 1 (Defr1) is allelic to Defb8 and chemoattracts immature DC and CD4+ T cells independently of CCR6
Authors: Taylor Karen , Rolfe Mark , Reynolds Natalie , Kilanowski Fiona , Pathania Uday , Clarke Dave , Yang De , Oppenheim Joost , Samuel Kay , Howie Sarah , Barran Perdita , Macmillan Derek , Campopiano Dominic , Dorin Julia
Published: April 2009

β‐Defensins comprise a family of cationic, antimicrobial and chemoattractant peptides. The six cysteine canonical motif is retained throughout evolution and the disulphide connectivities stabilise the conserved monomer structure. A murine β‐defensin gene (Defr1) present in the main defensin cluster of C57B1/6 mice, encodes a peptide with only five of the canonical six cysteine residues. In other inbred strains of mice, the allele encodes Defb8, which has the six cysteine motif. We show here that in common with six cysteine β‐defensins, defensin‐related peptide 1 (Defr1) displays chemoattractant activity for CD4+ T cells and immature DC (iDC), but not mature DC cells or neutrophils. Murine Defb2 replicates this pattern of attraction. Defb8 is also able to attract iDC but not mature DC. Synthetic analogues of Defr1 with the six cysteines restored (Defr1 Y5C) or with only a single cysteine (Defr1‐1cV) chemoattract CD4+ T cells with reduced activity, but do not chemoattract DC. β‐Defensins have previously been shown to attract iDC through CC receptor 6 (CCR6) but neither Defr1 or its related peptides nor Defb8, chemoattract cells overexpressing CCR6. Thus, we demonstrate that the canonical six cysteines of β‐defensins are not required for the chemoattractant activity of Defr1 and that neither Defr1 nor the six cysteine polymorphic variant allele Defb8, act through CCR6.