bluuebunny/crossref_metadata_2025 huggingface dataset:
Synergy with Rifampin and Kanamycin Enhances Potency, Kill Kinetics, and Selectivity ofDeNovo-Designed Antimicrobial Peptides
Authors: Anantharaman Aparna , Rizvi Meryam Sardar , Sahal Dinkar
Published: February 2010

By choosing membranes as targets of action, antibacterial peptides offer the promise of providing antibiotics to which bacteria would not become resistant. However, there is a need to increase their potency against bacteria along with achieving a reduction in toxicity to host cells. Here, we report that threede novo-designed antibacterial peptides (ΔFm, ΔFmscr, and Ud) with poor to moderate antibacterial potencies and kill kinetics improved significantly in all of these aspects when synergized with rifampin and kanamycin againstEscherichiacoli. (ΔFm and ΔFmscr [a scrambled-sequence version of ΔFm] are isomeric, monomeric decapeptides containing the nonproteinogenic amino acid α,β-didehydrophenylalanine [ΔF] in their sequences. Ud is a lysine-branched dimeric peptide containing the helicogenic amino acid α-aminoisobutyric acid [Aib].) In synergy with rifampin, the MIC of ΔFmscr showed a 34-fold decrease (67.9 μg/ml alone, compared to 2 μg/ml in combination). A 20-fold improvement in the minimum bactericidal concentration of Ud was observed when the peptide was used in combination with rifampin (369.9 μg/ml alone, compared to 18.5 μg/ml in combination). Synergy with kanamycin resulted in an enhancement in kill kinetics for ΔFmscr (no killing until 60 min for ΔFmscr alone, versus 50% and 90% killing within 20 min and 60 min, respectively, in combination with kanamycin). Combination of the dendrimeric peptide ΔFq (a K-K2 dendrimer for which the sequence of ΔFm constitutes each of the four branches) (MIC, 21.3 μg/ml) with kanamycin (MIC, 2.1 μg/ml) not only lowered the MIC of each by 4-fold but also improved the therapeutic potential of this highly hemolytic (37% hemolysis alone, compared to 4% hemolysis in combination) and cytotoxic (70% toxicity at 10× MIC alone, versus 30% toxicity in combination) peptide. Thus, synergy between peptide and nonpeptide antibiotics has the potential to enhance the potency and target selectivity of antibacterial peptides, providing regimens which are more potent, faster acting, and safer for clinical use.
Mechanism of Resistance of Hepatitis C Virus Replicons to Structurally Distinct Cyclophilin Inhibitors
Authors: Puyang Xiaoling , Poulin Danielle L. , Mathy Joanna E. , Anderson Leah J. , Ma Sue , Fang Zheng , Zhu Shejin , Lin Kai , Fujimoto Roger , Compton Teresa , Wiedmann Brigitte
Published: February 2010

The current standard of care for hepatitis C virus (HCV) infection, pegylated alpha interferon in combination with ribavirin, has a limited response rate and adverse side effects. Drugs targeting viral proteins are in clinical development, but they suffer from the development of high viral resistance. The inhibition of cellular proteins that are essential for viral amplification is thought to have a higher barrier to the emergence of resistance. Three cyclophilin inhibitors, the cyclosporine analogs DEBIO-025, SCY635, and NIM811, have shown promising results for the treatment of HCV infection in early clinical trials. In this study, we investigated the frequency and mechanism of resistance to cyclosporine (CsA), NIM811, and a structurally unrelated cyclophilin inhibitor, SFA-1, in replicon-containing Huh7 cells. Cross-resistance between all clones was observed. NIM811-resistant clones were selected only after obtaining initial resistance to either CsA or SFA-1. The time required to select resistance against cyclophilin inhibitors was significantly longer than that required for resistance selection against viral protein inhibitors, and the achievable resistance level was substantially lower. Resistance to cyclophilin inhibitors was mediated by amino acid substitutions in NS3, NS5A, and NS5B, with NS5A mutations conferring the majority of resistance. Mutation D320E in NS5A mediated most of the resistance conferred by NS5A. Taken together, the results indicate that there is a very low frequency and level of resistance to cyclophilin-binding drugs mediated by amino acid substitutions in three viral proteins. The interaction of cyclophilin with NS5A seems to be the most critical, since the NS5A mutations have the largest impact on resistance.
Quantitation of Azoles and Echinocandins in Compartments of Peripheral Blood by Liquid Chromatography-Tandem Mass Spectrometry
Authors: Farowski Fedja , Cornely Oliver A. , Vehreschild Jörg J. , Hartmann Pia , Bauer Tim , Steinbach Angela , Rüping Maria J. G. T. , Müller Carsten
Published: February 2010

A rapid turnaround is a prerequisite of therapeutic drug monitoring (TDM). For antifungals, this need is still unmet, since hardly any method has been established to simultaneously quantitate concentrations of different antifungal classes. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed allowing quantitation of anidulafungin (ANF), caspofungin (CSF), isavuconazole (ISC), micafungin (MCF), posaconazole (PSC), and voriconazole (VRC). Quantitation was successful with diluted plasma samples, peripheral blood mononuclear cells (PBMC), polymorphonuclear leukocytes (PMN), and erythrocytes (RBC). A triple quadrupole mass spectrometer in selected reaction monitoring mode was used with positive electrospray ionization. Cells and calibration standards were extracted with acetonitrile containing internal standard. Internal standards were a CSF derivate for echinocandins and itraconazole for triazoles. Chromatographic separation of the supernatant was achieved by a gradient method facilitating a BetaBasic C4 column. Analytes were quantified in a single 8-min run. Calibration curves were linear and fitted using least squares with a weighting factor of the reciprocal concentration. Limits of detection (ng/ml) were ANF, 8.3; CSF, 31.5; ISC, 1.5; MCF, 97.7; PSC, 3.3; and VRC, 1.4. The lower limits of quantitation (ng/ml) were ANF, 64; CSF, 108; ISC, 4.5; MCF, 160; PSC, 10; and VRC, 4.2. Intraday precisions ranged from 6.3% to 8.8% for azoles and 8.8% to 15.4% for echinocandins. Intraday and interday accuracies (percent bias) of all analytes were within 13.8%. The method was established as standard practice for the quantitation of intracellular antifungal concentrations and optimizes TDM by applying a rapid single method for 6 antifungals.
Involvement of the Beta Subunit of RNA Polymerase in Resistance to Streptolydigin and Streptovaricin in the Producer OrganismsStreptomyces lydicusandStreptomyces spectabilis
Authors: Sánchez-Hidalgo Marina , Núñez Luz Elena , Méndez Carmen , Salas José A.
Published: February 2010

Streptomyces lydicusNRRL2433 andS. spectabilisNRRL2494 produce two inhibitors of bacterial RNA polymerase: the 3-acyltetramic acid streptolydigin and the naphthalenic ansamycin streptovaricin, respectively. Both strains are highly resistant to their own antibiotics. Independent expression of theS. lydicusandS. spectabilis rpoBandrpoCgenes, encoding the β- and β′-subunits of RNA polymerase, respectively, inS. albusshowed that resistance is mediated byrpoB, with no effect ofrpoC. Within the β-subunit, resistance was confined to an amino acid region harboring the “rif region.” Comparison of the β-subunit amino acid sequences of this region from the producer strains and those of other streptomycetes and site-directed mutagenesis of specific differential residues located in it (L485 and D486 inS. lydicusand N474 and S475 inS. spectabilis) showed their involvement in streptolydigin and streptovaricin resistance. Other amino acids located close to the “Stl pocket” in theS. lydicusβ-subunit (L555, F593, and M594) were also found to exert influence on streptolydigin resistance.
Comparison of two correction methods for the bias due to the logarithmic transformation in the estimation of biomass
Authors: Lee C. Y.
Published: February 2010

Finney's method and the method of maximum likelihood for correcting the bias due to the logarithmic transformation in the estimation of biomass are presented as step-by-step procedures and are compared using empirical data and statistical theory. Based on theoretical considerations, ease of computation, and the use of empirical data, the method of maximum likelihood is recommended.
Dormancy in Abiesfraseri seedlings at the end of the first growth cycle
Authors: Hinesley L. E.
Published: February 2010

Two experiments were conducted to examine the effect of chilling duration and postchilling photoperiod on breaking dormancy in Fraser fir (Abiesfraseri (Pursh) Poir.) seedlings. Chilling durations were 0, 2, 4, 6, 8, 10, or 12 weeks at 4 °C. Five postchilling photoperiods were used: 9, 12, 15, and 18 h, or a9-h natural day plus a3-h night light break with incandescent light.Rest in Fraser fir seedlings is shallow at the end of the first growth cycle. Dormant containerized plants outplanted in the spring grew abnormally, and resumed normal growth only after experiencing a winter. Those chilled 2 or more weeks broke dormancy rapidly under controlled-environment conditions and grew well under photoperiods > 15 h. Shoot elongation increased with day length, but not linearly. One-year-old seedlings taken from an outdoor nursery in early October broke dormancy under 9-h days in a greenhouse only after 4 weeks of chilling. A night light break resulted in 100% budbreak, even in nonchilled plants. Time to budbreak decreased with increasing duration of chilling. Dry matter increased linearly with chilling duration and was greatest under long days. Less chilling was required for budbreak than for maximum shoot elongation or dry matter production. Four to 6 weeks of chilling was sufficient to overcome rest.
FROM GLOBAL SYMMETRIES TO LOCAL CURRENTS: THE FREE (SCALAR) CASE IN FOUR DIMENSIONS
Authors: MORSELLA GERARDO , TOMASSINI LUCA
Published: February 2010

Within the framework of algebraic quantum field theory, we propose a new method of constructing local generators of (global) gauge symmetries in field theoretic models, starting from the existence of unitary operators implementing locally the flip automorphism on the doubled theory. We show, in the simple example of the internal symmetries of a multiplet of free scalar fields, that through the pointlike limit of such local generators the conserved Wightman currents associated with the symmetries are recovered.
CONTROL OF n-SCROLL CHUA'S CIRCUIT
Authors: BOUKABOU ABDELKRIM , SAYOUD BILEL , BOUMAIZA HAMZA , MANSOURI NOURA
Published: February 2010

This paper addresses the control of unstable fixed points and unstable periodic orbits of the n-scroll Chua's circuit. In a first step, we give necessary and sufficient conditions for exponential stabilization of unstable fixed points by the proposed predictive control method. In addition, we show how a chaotic system with multiple unstable periodic orbits can be stabilized by taking the system dynamics from one UPO to another. Control performances of these approaches are demonstrated by numerical simulations.
HYPERCHAOS BASED IMAGE ENCRYPTION
Authors: GANGADHAR CH. , DEERGHA RAO K.
Published: February 2010

Chaos based encryption may offer new quality in secure data transmission. A recently proposed Chaotic-Key Based Algorithm (CKBA) has been shown to be unavoidably susceptible to chosen/known-plaintext attacks and ciphertext-only attacks. In this paper, Hyper Chaotic-Key Based Algorithm (HCKBA) using hyper chaos is proposed to enhance the security of CKBA. The enhanced security of the proposed algorithm is analyzed through cryptanalysis. Further, VLSI architecture of the proposed algorithm is designed. The VLSI architecture is implemented on an image using XILINX's ModelSim to demonstrate the effectiveness of the proposed scheme.
Comparing lighting quality evaluations of real scenes with those from high dynamic range and conventional images
Authors: Newsham Guy R. , Cetegen Duygu , Veitch Jennifer A. , Whitehead Lorne
Published: February 2010

Thirty-nine participants viewed six interior scenes in an office/laboratory building and rated them for brightness, uniformity, pleasantness, and glare. The scenes were viewed in three presentation modes: participants saw the real space and images of the spaces on a 17-inch computer monitor in both conventional and high dynamic range (HDR) mode. HDR mode allowed the high range of luminances in the real scene to be accurately reproduced, with maximum luminances more than 10 times higher than those in the conventional images. For those participants who saw the images before the real spaces (the most relevant order for practical applications), the HDR images were rated as significantly more realistic than the conventional images. However, this effect was limited to scenes with relatively large areas of high luminance, which in this study was represented by scenes with windows and daylight. Ratings of the HDR images were significantly related to simple photometric descriptors of the images in the expected manner: Brightness and glare ratings were positively correlated with overall and elevated luminance, and nonuniformity ratings were positively correlated with luminance variability. These results suggest that for evaluations of visual appearance of interior scenes featuring large areas of high luminance, the HDR method may be used as a surrogate for experiencing a real space both for lighting quality research, and in the design process.
The MACODO middleware for context-driven dynamic agent organizations
Authors: Weyns Danny , Haesevoets Robrecht , Helleboogh Alexander , Holvoet Tom , Joosen Wouter
Published: February 2010

One of the major challenges in engineering distributed multiagent systems is the coordination necessary to align the behavior of different agents. Decentralization of control implies a style of coordination in which the agents cooperate as peers with respect to each other and no agent has global control over the system, or global knowledge about the system. The dynamic interactions and collaborations among agents are usually structured and managed by means of roles and organizations. In existing approaches agents typically have a dual responsibility: on the one hand playing roles within the organization, on the other hand managing the life-cycle of the organization itself, for example, setting up the organization and managing organization dynamics. Engineering realistic multiagent systems in which agents encapsulate this dual responsibility is a complex task.

In this article, we present a middleware for context-driven dynamic agent organizations. The middleware is part of an integrated approach, called MACODO: Middleware Architecture for COntext-driven Dynamic agent Organizations. The complementary part of the MACODO approach is an organization model that defines abstractions to support application developers in describing dynamic organizations, as described in Weyns et al. [2010].

The MACODO middleware offers the life-cycle management of dynamic organizations as a reusable service separated from the agents, which makes it easier to understand, design, and manage dynamic organizations in multiagent systems. We give a detailed description of the software architecture of the MADOCO middleware. The software architecture describes the essential building blocks of a distributed middleware platform that supports the MACODO organization model. We used the middleware architecture to develop a prototype middleware platform for a traffic monitoring application. We evaluate the MACODO middeware architecture by assessing the adaptability, scalability, and robustness of the prototype platform.
Cooperation through self-similar social networks
Authors: Allen Stuart M. , Colombo Gualtiero , Whitaker Roger M.
Published: February 2010

We address the problem of cooperation in decentralized systems, specifically looking at interactions between independent pairs of peers where mutual exchange of resources (e.g., updating or sharing content) is required. In the absence of any enforcement mechanism or protocol, there is no incentive for one party to directly reciprocate during a transaction with another. Consequently, for such decentralized systems to function, protocols for self-organization need to explicitly promote cooperation in a manner where adherence to the protocol is incentivized.

In this article we introduce a new generic model to achieve this. The model is based on peers repeatedly interacting to build up and maintain a dynamic social network of others that they can trust based on similarity of cooperation. This mechanism effectively incentivizes unselfish behavior, where peers with higher levels of cooperation gain higher payoff. We examine the model's behavior and robustness in detail. This includes the effect of peers self-adapting their cooperation level in response to maximizing their payoff, representing a Nash-equilibrium of the system. The study shows that the formation of a social network based on reflexive cooperation levels can be a highly effective and robust incentive mechanism for autonomous decentralized systems.
Electrical and Structural Characterization of Epitaxial-Grown Mg-Doped C60 Thin Films
Authors: Kojima Nobuaki , Natori Masato , Yamaguchi Masafumi
Published: February 2010

The epitaxial growth of Mg-doped C60 films has been investigated. It is found that the epitaxial growth of Mg-doped C60 film is enabled by using mica (001) substrate in the low Mg concentration region (Mg/C60 molar ratio < 1). The crystal quality of the epitaxial Mg-doped C60 film is improved drastically in compared with micro-crystalline film on glass substrate. Such drastic improvement of crystal quality in the epitaxial films results significant increase in conductivity. This result may indicate the significant increase of carrier mobility.
Electrochemical Quartz Crystal Microbalance Technique in Sonoelectrochemistry
Authors: Schneider Oliver , Martens Sladjana , Argirusis Christos
Published: February 2010

The influence of the experimental conditions on the operation of a quartz crystal microbalance in an ultrasonic field was studied in water and different Cu electrolytes. An increase of the ultrasonic intensity and a decreasing distance between the ultrasonic horn tip and the surface of the quartz resonator caused an increase in signal noise and a decrease in the resonance frequency without disturbing the measurements strongly. Surface cavitation was found to impact the quartz response significantly and led to a roughening of its gold electrode.
Benzoin Condensation in Ionic Liquids via Electrochemical Generation of Carbene
Authors: Chiarotto Isabella , Feroci Marta , Orsini Monica , Sotgiu Giovanni , Rossi Leucio
Published: February 2010

Herein we report the use of N-Heterocyclic carbenes, generated by electrolysis, as organocatalysts in the benzoin condensation reaction. The effect of various electrochemical and physical parameters was studied, and the procedure was carried out using various aromatic, and heteroaromatic aldehydes. The use of classical solvents as well as any addition of bases was avoided.
An Electrocatalytic System that Mimics the Catalytic Oxidation of Biogenic Mono- and Polyamines by Semicarbazide-sensitive Amine Oxidases (SSAOs)
Authors: Largeron Martine , Fleury Maurice-Bernard , Strolin Benedetti Margherita
Published: February 2010

Chemoselective oxidation of primary aliphatic biogenic mono- and polyamines into imines has been successfully achieved, under metal-free conditions, by using an electrocatalytic system that mimics the activity of semicarbazide-sensitive amine oxidase (SSAO) enzymes. Accordingly, high catalytic performance was observed with unbranched primary amines such as methylamine and aminoacetone, and with the primary amino groups of diamines and polyamines like putrescine and spermidine, all of them being reference substrates for SSAO enzymes. Furthermore, contrary to flavin-adenine dinucleotide (FAD)-dependent amine oxidase enzymes, no activity was found with secondary and tertiary amines. Finally, when compared with the direct electrochemical oxidation of primary aliphatic amines, which occurs at high anodic potential (Ean > + 1.5 V vs SCE) and led to unstable cation radicals that rapidly deprotonate and attach to the electrode surface (Pt, carbon), 1.0 V was gained using this electrocatalytic process (Ean = + 0.5 V vs SCE).
Screening of the Fluorination Parameters to Improve the Oxidation Resistance of Ni-Base Superalloys at Elevated Temperatures
Authors: Zschau Hans-Eberhard , Masset Patrick J. , Schütze Michael
Published: February 2010

The halogen effect was applied to improve the oxidation resistance of Ni-base superalloys with low Al-content. By increasing the Al-activity on the metal surface the formation of a dense protective alumina scale becomes possible. Thermodynamic calculations show the existence of a positive fluorine effect for the alloy IN738 for temperatures between 900C and 1200C. Ion implantation was applied for the screening of the corresponding fluorine concentrations. The change of the oxidation mechanism was achieved from an inward growing non-protective discontinuous to a dense protective alumina scale. The optimum implantation parameters were identified.
Oxidation Tests with Untreated and F-Treated TNBV5 Alloys
Authors: Masset Patrick J. , Schütze Michael
Published: February 2010

In this work three fluorination treatments were applied to the alloy TNBV5 to improve its oxidation behavior (halogen effect). The fluorination as well as the resulting oxidation behavior in air is described. Oxidation testing in complex atmosphere (air + 0.1 vol% SO2) was carried out with F-treated specimens. The results show in that all the cases the halogen effect is effective and leads to the formation of an almost pure and adherent alumina layer.
Direct Heating for Analysing Reforming Reaction on Alloy Surface in Low S/C Environment
Authors: Ueda Mitsutoshi , Fujita Kenjiro , Matsuzaki Yoshio , Maruyama Toshio
Published: February 2010

New apparatus for direct heating of alloy specimen in the gas stream has been developed in order to analyze not only reforming reaction but also carbon deposition on the alloy surface in low S/C environment. A foil of iron can be heated directly to 1073 K by the Joule heat from the specimen. Temperature of the foil can be kept at 1073 plus-minus 10 K by using AC power regulator connected with temperature controller. Temperature of the foil is not influenced by the thermal radiation from the oxide scale during the oxidation. One experiment has been carried out to check carbon deposition on the ferritic alloys at 1073 K in the CH4-H2O gas mixture. Oxidation and carbon deposition simultaneously occur on the alloy surface and no carbon deposition is observed in the chamber. Developed apparatus is suitable for investigation of carbon deposition and carburization of alloys in low S/C environment.
Effect of Niobium Additions on the Oxidation Behavior of Stainless Steels for SOFC Interconnects
Authors: Fergus Jeffrey W. , Zhao Yu , Haney Ricky , Cramer Kirn , Riherd Lynne
Published: February 2010

Ferritic stainless steels are the most promising low-cost interconnect material for solid oxide fuel cells. The performances of two prospective interconnect alloys, 430 and 441, differ in dual atmosphere exposures, in which the alloy is exposed to hydrogen on one side and air on the other. The two alloys are similar in composition, with the same chromium content, but alloy 441 contains small amounts of niobium and titanium. The differences in behavior are typically attributed to the niobium addition, so in this work a diffusion treatment was used to introduce niobium into alloy 430, and the oxidation behavior of the niobium-doped alloy 430 were compared with those of undoped alloy 430 and alloy 441.
Oxidation Behaviors of SiGe Nanowire Arrays Fabricated by Au-Assisted Wet Chemical Etching
Authors: Lai C. C. , Lin J. S. , Cheng S. L. , Lee Sheng-Wei
Published: February 2010

This study investigates the oxidation behaviors of Si0.95Ge0.05 nanowire arrays fabricated by combining nanosphere lithography and Au-assisted chemical etching. After oxidation at 450° for 8 hours, the diameter of SiGe nanowires can be reduced from 360 nm to 250 nm. Furthermore, the SiGe nanowires were transformed into the taper-like structures with a deep trench around the bottom regions after oxidation. We elucidate these phenomena in terms of the nonuniform oxidation rate caused by the nonuniform oxygen ambient and the Au-Si-Ge eutectic alloying. This work provides an effective approach to design the low-dimensional SiGe-based nanostructures for possible applications.
Electrochemiluminescence and Charge Transport Properties of Metallopolymer-Gold Nanocomposites
Authors: Devadoss Anitha , Dickinson Calum , Keyes Tia E. , Forster Robert J.
Published: February 2010

Metallopolymer-gold nanocomposites were prepared by mixing 4-(dimethylamino) pyridine protected gold nanoparticles (diameter approximately 5{plus minus}0.5 nm) and [Ru(bpy)2PVP10](ClO4)2, at different mole ratios where bpy is 2,2'-bipyridyl and PVP is poly(4-vinylpyridine). The photoluminescence emission intensity of the metallopolymer is quenched approximately 72% at AuNP:Ru molar ratio of 12.5x10-2. The electrochemical and the electrochemiluminescence (ECL) properties of thin layers of the nanocomposites are reported. Significantly, despite the ability of the metal nanoparticles to quench the ruthenium based emission in solution, the electrochemiluminescence of the optimized nanocomposite films (mole ratio 6.24x10-2) is approximately 3.5 times greater than that of the parent metallopolymer. This enhancement arises from the increased rate of charge transport through the thin films that leads to a greater number of excited states per unit time while minimizing the quenching effects.
Electrodeposition of Cu+PdO and (Cu-Pd)+PdO Composites
Authors: Verlato Enrico , Cattarin Sandro , Comisso Nicola , Gerbasi Rosalba , Guerriero Paolo , Musiani Marco , Vázquez-Gómez Lourdes
Published: February 2010

The co-deposition of PdO particles with a Cu matrix has been investigated with the aim of extending the composite deposition procedure to the preparation of materials potentially capable of catalyzing the low-temperature combustion of methane and other low hydrocarbons. Cu+PdO composites with a low dispersed phase content were obtained from either basic pyrophosphate or acid sulfate baths. PdO incorporation in Cu-Pd alloy matrices was much more effective than incorporation in Cu matrices, yielding deposits with 20-25 Pd at %, even when the Pd content of the alloys was as low as 1-2 at %. (Cu-Pd)+PdO composites were highly porous and mechanically stable.
Electrocatalytic Properties of a Novel Platinumpolytyramine Composite Electrode Material
Authors: Spătaru Tant¸a , Marcu Maria , Spătaru Nicolae
Published: February 2010

A platinum-polytyramine (PTy) composite material was obtained by potentiodynamic deposition of PTy, followed by Pt electrodeposition. The polytyramine layers were used as a matrix for electrochemical deposition of platinum and the electrocatalytic activity for methanol oxidation of the composite material thus obtained was putted into evidence. It also appeared that, when deposited in the PTy matrix, Pt nanoparticles are less sensitive to deactivation compared to Pt on graphite.
AC Impedance Characterization of Highly Resistive Media Using Four-Electrode Electrochemical Cells
Authors: Lvovich Vadim , Smiechowski Matthew
Published: February 2010

Electrochemical impedance spectroscopy (EIS) was employed for characterization studies of highly resistive non-aqueous media using four-electrode cells with solid state reference electrodes. The influence of internal resistance of the impedance analyzer, the media's temperature and conductivity, shielding of the cables, and the electrochemical cell geometry and configuration on the impedance results were investigated. The most accurate EIS measurements can be made in the 2-electrode cells with active shields where a single arc at high frequencies and a complicated low frequency interfacial impedance feature were observed. When 4-electrode cells were employed, the relative impedances of the sample and the analyzer, geometry and positioning of voltage electrodes, and capacitive coupling between the signal lines introduced two types of impedance measurement artifacts. A capacitive-resistive low frequency load was interpreted as a measurement artifact originating from the voltage electrodes' geometry and positioning. The medium frequency artifact combining resistive, capacitive and inductive features is intrinsic to the experimental setup resulting in a voltage divider effect.
Blocking Non-Specific Uptake of Engineered Nanomaterials
Authors: Aguilar Zoraida P. , Xu Hengyi , Dixon John , Wang Andrew
Published: February 2010

Engineered nanomaterials (eNMs) are dominating the 21st century in industrial, biological, and medical applications. ENMs are the emerging new materials for sunscreens, medical imaging , solar cell, cosmetics, sports gadgets, consumer products, as well as biological detection materials. One of the major concerns in the application of ENMs like quantum dots (QDs) in life sciences research and clinical diagnostics is non-specific binding (NSB) or nonspecific uptake (NSU) in biological materials such as cells, proteins, or DNA. Elimination of non-specific uptake of ENMs is essential in order to utilize the maximum potential for detection of different biological molecules resulting from the >50% higher emission intensity of QDs in comparison with organic dyes. Furthermore, ENMs are small enough to be used in biological systems making them useful for clinical applications such as drug delivery and/or magnetic resonance imaging. Since QDs are size tunable they can be modified for the detection of single or multiple analyte. However, NSU and/or NSB must be minimized or eliminated before these can be used for the detection of biological analytes. Studies on the development of blocking buffers to minimize or eliminate NSB/NSU have been initiated. Blockers such as bovine serum albumin, polyvinyl pyrrolidone and detergents such as tween 20 and triton X 100 have been used to minimize NSB/NSU. Results of blocking nonspecific uptake of ENMs will be discussed.
Effect of the Ionic Strength and the Electrolyte Composition on the Suppression of Copper Deposition by PEG
Authors: Atanasova Tanya A. , Strubbe Katrien , Vereecken Philippe M.
Published: February 2010

The acid copper sulfate solutions used for Damascene plating contain several additives which provide the differential kinetics inside cavities for void-free fill. Although the synergetic effects between these additives were studied quite thoroughly for the last 2 decades, the underlying mechanisms are still not fully understood. In this work we provide some further insight into the physicochemical mechanism of copper deposition inhibition by the suppressor polymer. The quantitative participation of each solution component in the formation of Cu(I)-Suppressor-Cl complex is examined. In addition, our experiments show that ionic strength has a profound effect on the adsorption/desorption mechanism.
Common Fixed Point Theorem in Partially Ordered "Equation missing" -Fuzzy Metric Spaces
Authors: Shakeri S , Ćirić LJB , Saadati R
Published: February 2010

We introduce partially ordered "Equation missing"-fuzzy metric spaces and prove a common fixed point theorem in these spaces.
Ventilatory Efficiency and the Selection of Patients for Heart Transplantation
Authors: Ferreira António M. , Tabet Jean-Yves , Frankenstein Lutz , Metra Marco , Mendes Miguel , Zugck Christian , Beauvais Florence , Cohen-Solal Alain
Published: February 2010

Background—

Ventilatory efficiency, assessed by the slope of minute ventilation (V
e
) versus carbon dioxide production (V
co
2
), is a powerful prognostic marker in patients with chronic heart failure. We hypothesized that V
e
/V
co
2
slope would be more accurate than the current listing criteria for heart transplantation (HTx) in identifying patients likely to derive a survival benefit from this intervention.

Methods and Results—

A total of 663 patients with chronic heart failure who underwent cardiopulmonary exercise testing were tracked for cardiac mortality and HTx. V
e
/V
co
2
slope was the strongest independent predictor of mortality. Using a V
e
/V
co
2
slope threshold instead of the current exercise criteria would classify 39 more subjects as being high risk (196 versus 157), correctly identifying 19 more patients who died during follow-up (57 versus 38) and 16 others who underwent transplantation (52 versus 36). Unlike the current listing criteria for HTx, V
e
/V
co
2
slope provided significant discrimination between the 3-year survival of high- and low-risk patients and posttransplant patients selected from the International Society for Heart and Lung Transplantation registry. Reanalysis of survival data using death or HTx as the end point showed similar results.

Conclusions—

V
e
/V
co
2
slope is more accurate than the current listing criteria for HTx in identifying patients likely to derive a survival benefit from HTx.
Measurement Precision in the Optimization of Cardiac Resynchronization Therapy
Authors: Turcott Robert G. , Witteles Ronald M. , Wang Paul J. , Vagelos Randall H. , Fowler Michael B. , Ashley Euan A.
Published: February 2010

Background—

Cardiac resynchronization therapy improves morbidity and mortality in appropriately selected patients. Whether atrioventricular (AV) and interventricular (VV) pacing interval optimization confers further clinical improvement remains unclear. A variety of techniques are used to estimate optimum AV/VV intervals; however, the precision of their estimates and the ramifications of an imprecise estimate have not been characterized previously.

Methods and Results—

An objective methodology for quantifying the precision of estimated optimum AV/VV intervals was developed, allowing physiologic effects to be distinguished from measurement variability. Optimization using multiple conventional techniques was conducted in individual sessions with 20 patients. Measures of stroke volume and dyssynchrony were obtained using impedance cardiography and echocardiographic methods, specifically, aortic velocity-time integral, mitral velocity-time integral, A-wave truncation, and septal-posterior wall motion delay. Echocardiographic methods yielded statistically insignificant data in the majority of patients (62%–82%). In contrast, impedance cardiography yielded statistically significant results in 84% and 75% of patients for AV and VV interval optimization, respectively. Individual cases demonstrated that accepting a plausible but statistically insignificant estimated optimum AV or VV interval can result in worse cardiac function than default values.

Conclusions—

Consideration of statistical significance is critical for validating clinical optimization data in individual patients and for comparing competing optimization techniques. Accepting an estimated optimum without knowledge of its precision can result in worse cardiac function than default settings and a misinterpretation of observed changes over time. In this study, only impedance cardiography yielded statistically significant AV and VV interval optimization data in the majority of patients.
Teratogen-induced alterations in microRNA-34, microRNA-125b and microRNA-155 expression: correlation with embryonic p53 genotype and limb phenotype
Authors: Gueta Keren , Molotski Natali , Gerchikov Natalie , Mor Eyal , Savion Shoshana , Fein Amos , Toder Vladimir , Shomron Noam , Torchinsky Arkady
Published: February 2010

Background

In a large number of studies, members of the microRNA (miRNA)-34 family such as miRNA-34a, miRNA-34b, miRNA-34c, as well as miRNA-125b and miRNA-155, have been shown to be regulators of apoptosis. The ability of these miRNAs to perform this function is mainly attributed to their ability to interact with the p53 tumor suppressor, which is a powerful regulator of the teratologic susceptibility of embryos. We chose to explore whether miRNA-34a/b/c, miRNA-125b and miRNA-155 may play a role in teratogenesis by using p53+/- pregnant mice treated with cyclophosphamide (CP) as a model. We evaluated how CP-induced alterations in the expression of these miRNAs in the embryonic limbs correlate with embryonic p53 genotype and CP-induced limb phenotypes.

Results

The limbs of p53 positive embryos were more sensitive to CP-induced teratogenic insult than the limbs of p53 negative embryos. The hindlimbs were more severely affected than the forelimbs. Robust miRNA-34a expression was observed in the fore- and hindlimbs of p53+/+ embryos exposed to 12.5 mg/kg CP. The dose of 20 mg/kg CP induced almost a two-fold increase in the level of miRNA-34a expression as compared to that exhibited by p53+/+ embryos exposed to a lower dose. Increased miRNA-34b and miRNA-34c expression was also observed. Of note, this dose activated miRNA-34a and miRNA-34c in the forelimbs of p53-/- embryos. When embryos were exposed to 40 mg/kg CP, the expression pattern of the miRNA-34a/b/c was identical to that registered in the limbs of embryos exposed to 20 mg/kg CP. However, this dose suppressed miRNA-125b and miRNA-155 expression in the fore- and hindlimbs of p53+/+ embryos.

Conclusion

This study demonstrates that teratogen-induced limb dysmorphogenesis may be associated with alterations in miRNA-34, miRNA-125b and miRNA-155 expression. It also suggests for the first time that p53-independent mechanisms exist contributing to teratogen-induced activation of miRNA-34a and miRNA-34c. At the same time, teratogen-induced suppression of miRNA-125b and miRNA-155 expression may be p53 dependent. The analysis of correlations between the expression pattern of the tested miRNAs and CP induced limb phenotypes implies that miRNAs regulating apoptosis may differ from each other with respect to their functional role in teratogenesis: some miRNAs act to protect embryos, whereas other miRNAs boost a teratogen-induced process of maldevelopment to induce embryonic death.
Making the diagnosis of Chronic Fatigue Syndrome/Myalgic Encephalitis in primary care: a qualitative study
Authors: Chew-Graham Carolyn , Dowrick Christopher , Wearden Alison , Richardson Victoria , Peters Sarah
Published: February 2010

Background

NICE guidelines emphasise the role of the primary care team in the management of patients with Chronic Fatigue Syndrome/Myalgic Encephalitis (CFS/ME). A key stage in effective management is making an accurate early diagnosis, supported by appropriate referral.

Methods

A nested qualitative study within a multi-centre randomised controlled trial which aimed to explore GPs' views on their role in making the diagnosis of CFS/ME and subsequent management of patients in primary care. Semi-structured interviews with 22 GPs. Interviews were transcribed verbatim and an iterative approach used to develop themes from the dataset.

Results

GPs described difficulties in defining CFS/ME and suggested that their role in making a diagnosis was to exclude physical causes for the patient's symptoms, but they reported little confidence in positively attributing the label of CFS/ME to a patient and their symptoms. GPs suggested that the label of CFS/ME could be potentially harmful for the patient. The role of referral to secondary care was debated and GPs struggled defining their own role in management of this group of patients.

Conclusions

Until GPs feel comfortable making the diagnosis of CFS/ME and facilitating initial management, and have appropriate services to refer patients to, there will continue to be delays in confirming the diagnosis and patients presenting in primary care with fatigue may not receive appropriate care.

Trial Registration

ISRCTN 74156610
Study of the serotonin transporter (SLC6A4) and BDNF genes in French patients with non syndromic mental deficiency
Authors: Tabagh Refaat , Andres Christian R , Védrine Sylviane , Cherpi-Antar Catherine , Thepault Rose-Anne , Mignon Laurence , Dufour-Rainfray Diane , Moraine Claude , Vourc'h Patrick
Published: February 2010

Background

Mental deficiency has been linked to abnormalities in cortical neuronal network connectivity and plasticity. These mechanisms are in part under the control of two interacting signalling pathways, the serotonergic and the brain-derived neurotrophic (BDNF) pathways. The aim of the current paper is to determine whether particular alleles or genotypes of two crucial genes of these systems, the serotonin transporter gene (SLC6A4) and the brain-derived neurotrophic factor gene (BDNF), are associated with mental deficiency (MD).

Methods

We analyzed four functional polymorphisms (rs25531, 5-HTTLPR, VNTR, rs3813034) of the SLC6A4 gene and one functional polymorphism (Val66 Met) of the BDNF gene in 98 patients with non-syndromic mental deficiency (NS-MD) and in an ethnically matched control population of 251 individuals.

Results

We found no significant differences in allele and genotype frequencies in the five polymorphisms studied in the SLC6A4 and BDNF genes of NS-MD patients versus control patients. While the comparison of the patterns of linkage disequilibrium (D') in the control and NS-MD populations revealed a degree of variability it did not, however, reach significance. No significant differences in frequencies of haplotypes and genotypes for VNTR/rs3813034 and rs25531/5-HTTLPR were observed.

Conclusion

Altogether, results from the present study do not support a role for any of the five functional polymorphisms of SLC6A4 and BDNF genes in the aetiology of NS-RM. Moreover, they suggest no epistatic interaction in NS-MD between polymorphisms in BDNF and SLC6A4. However, we suggest that further studies on these two pathways in NS-MD remain necessary.
Identification of hypoxanthine as a urine marker for non-Hodgkin lymphoma by low-mass-ion profiling
Authors: Yoo Byong Chul , Kong Sun-Young , Jang Sang-Geun , Kim Kyung-Hee , Ahn Sun-A , Park Weon-Seo , Park Sohee , Yun Tak , Eom Hyeon-Seok
Published: February 2010

Background

Non-Hodgkin lymphoma (NHL) is a hematologic malignancy for which good diagnostic markers are lacking. Despite continued improvement in our understanding of NHL, efforts to identify diagnostic markers have yielded dismal results. Here, we translated low-mass-ion information in urine samples from patients with NHL into a diagnostic marker.

Methods

To minimize experimental error, we tested variable parameters before MALDI-TOF analysis of low-mass ions in urine. Urine from 30 controls and 30 NHL patients was analyzed as a training set for NHL prediction. All individual peak areas were normalized to total area up to 1000 m/z. The training set analysis was repeated four times. Low-mass peaks that were not affected by changes in experimental conditions were collected using MarkerView™ software. Human Metabolome Database (HMDB) searches and ESI LC-MS/MS analyses were used to identify low-mass ions that exhibited differential patterns in control and NHL urines. Identified low-mass ions were validated in a blinded fashion in 95 controls and 66 NHL urines to determine their ability to discriminate NHL patients from controls.

Results

The 30 highest-ranking low-mass-ion peaks were selected from the 60-urine training set, and three low-mass-ion peaks with high intensity were selected for identification. Of these, a 137.08-m/z ion showed lower mass-peak intensity in urines of NHL patients, a result that was validated in a 161-urine blind validation set (95 controls and 66 NHL urines). The 130.08-m/z ion was identified from HMDB searches and ESI LC-MS/MS analyses as hypoxanthine (HX). The HX concentration in urines of NHL patients was significantly decreased (P < 0.001) and was correlated with the mass-peak area of the 137.08-m/z ion. At an HX concentration cutoff of 17.4 μM, sensitivity and specificity were 79.2% and 78.4%, respectively.

Conclusions

The present study represents a good example of low-mass-ion profiling in the setting of disease screening using urine. This technique can be a powerful non-invasive diagnostic tool with high sensitivity and specificity for NHL screening. Furthermore, HX identified in the study may be a useful single urine marker for NHL screening.
Cyclooxygenase-2 enhances α2β1 integrin expression and cell migration via EP1 dependent signaling pathway in human chondrosarcoma cells
Authors: Liu Ju-Fang , Fong Yi-Chin , Chang Chih-Shiang , Huang Chun-Yin , Chen Hsien-Te , Yang Wei-Hung , Hsu Chin-Jung , Jeng Long-Bin , Chen Chih-Yi , Tang Chih-Hsin
Published: February 2010

Background

Cyclooxygenase (COX)-2, the inducible isoform of prostaglandin (PG) synthase, has been implicated in tumor metastasis. Interaction of COX-2 with its specific EP receptors on the surface of cancer cells has been reported to induce cancer invasion. However, the effects of COX-2 on migration activity in human chondrosarcoma cells are mostly unknown. In this study, we examined whether COX-2 and EP interaction are involved in metastasis of human chondrosarcoma.

Results

We found that over-expression of COX-2 or exogenous PGE2 increased the migration of human chondrosarcoma cells. We also found that human chondrosarcoma tissues and chondrosarcoma cell lines had significant expression of the COX-2 which was higher than that in normal cartilage. By using pharmacological inhibitors or activators or genetic inhibition by the EP receptors, we discovered that the EP1 receptor but not other PGE receptors is involved in PGE2-mediated cell migration and α2β1 integrin expression. Furthermore, we found that human chondrosarcoma tissues expressed a higher level of EP1 receptor than normal cartilage. PGE2-mediated migration and integrin up-regulation were attenuated by phospholipase C (PLC), protein kinase C (PKC) and c-Src inhibitor. Activation of the PLCβ, PKCα, c-Src and NF-κB signaling pathway after PGE2 treatment was demonstrated, and PGE2-induced expression of integrin and migration activity were inhibited by the specific inhibitor, siRNA and mutants of PLC, PKC, c-Src and NF-κB cascades.

Conclusions

Our results indicated that PGE2 enhances the migration of chondrosarcoma cells by increasing α2β1 integrin expression through the EP1/PLC/PKCα/c-Src/NF-κB signal transduction pathway.
Associations between attributes of live poultry trade and HPAI H5N1 outbreaks: a descriptive and network analysis study in northern Vietnam
Authors: Soares Magalhães Ricardo J , Ortiz-Pelaez Angel , Thi Kim Lan Lai , Dinh Quoc Hoang , Otte Joachim , Pfeiffer Dirk U
Published: February 2010

Background

The structure of contact between individuals plays an important role in the incursion and spread of contagious diseases in both human and animal populations. In the case of avian influenza, the movement of live birds is a well known risk factor for the geographic dissemination of the virus among poultry flocks. Live bird markets (LBM's) contribute to the epidemiology of avian influenza due to their demographic characteristics and the presence of HPAI H5N1 virus lineages. The relationship between poultry producers and live poultry traders (LPT's) that operate in LBM's has not been adequately documented in HPAI H5N1-affected SE Asian countries. The aims of this study were to document and study the flow of live poultry in a poultry trade network in northern Vietnam, and explore its potential role in the risk for HPAI H5N1 during 2003 to 2006.

Results

Our results indicate that LPT's trading for less than a year and operating at retail markets are more likely to source poultry from flocks located in communes with a past history of HPAI H5N1 outbreaks during 2003 to 2006 than LPT's trading longer than a year and operating at wholesale markets. The results of the network analysis indicate that LPT's tend to link communes of similar infection status.

Conclusions

Our study provides evidence which can be used for informing policies aimed at encouraging more biosecure practices of LPT's operating at authorised LBM's. The results suggest that LPT's play a role in HPAI H5N1 transmission and may contribute to perpetuating HPAI H5N1 virus circulation amongst certain groups of communes. The impact of current disease prevention and control interventions could be enhanced by disseminating information about outbreak risk and the implementation of a formal data recording scheme at LBM's for all incoming and outgoing LPT's.