bluuebunny/crossref_metadata_2025 huggingface dataset:
A Method of Protecting Subsea Wellheads Against Environmental Hazards
Authors: Foden George P. , Fenemore Keith E. , Fraser William J.
Published: September 2011

This paper presents the evaluation of the risk of damage to subsea wellheads from fishing gear and oil related objects. It lists the alternative forms of protection considered and the selection of the most cost effective type.

Details are given of the design and installation of two protective covers in the North Sea.

It presents the development of the design based on experience gained leading to the installation of a third cover in the same area.
New Development in Subsea Production – The Modular Manifold Concept
Authors: Muller D. , Arnaudeau M. , Renard B.
Published: September 2011

Offshore development of oil or gas fields in deep waters (up to 1 000 m) involves floating facilities for process, subsea wellheads and connection between them by riser and manifold.

Many technical problems arise amongst which two can be easily solved by a modular manifold concept : they are flowline connection and maintenance of subsea equipment.

The basic idea of the concept is to split the manifold in modules which are recoverable and whose functions are:

– control of the production – connect one flowline, already laid and positioned with the manifold

The installation of the module is performed with drill pipe and hydraulic handling tool; all control equipment such as valves, connectors, hydraulic devices, are located on the module and can be easily serviced at surface; the geometry of the module is adapted to T.F.L. technique.

A prototype of such an equipment is presently built in France and sea trials of the concept including flowline connection on the manifold will be performed during winter 80/81.
Assessment of hot cracking behaviour in welds
Authors: Kannengiesser Thomas , Rethmeier Michael , Portella Pedro Dolabella , Ewert Uwe , Redmer Bernhard
Published: September 2011

Hot crack assessment during production and processing of metallic materials is an essential prerequisite for the safety of welded structures. The hot cracking investigations presented here were carried out as part of a study aimed at the development of Cr/Ni low transformation temperature filler materials. Low transformation temperature alloys open up the possibility for welding high strength steels. The externally loaded Modified Varestraint Transvarestraint hot cracking test was employed in the experiments described. The hot cracking resistance was evaluated with the help of light microscopy applied at the specimen surface. The proportionality between hot cracking susceptibility and Cr/Ni alloy content was explained by the altered solidification kinetics and by the enlarged solidification interval. The internal crack paths and the three-dimensional structure of the crack net in the material volume were examined using X-ray computer tomography. The total crack lengths for different material depths and circumjacent rectangular volumes, respectively, were be determined. An increasing hot cracking susceptibility with increasing Cr/Ni alloy content was also be established for the specimen volume.
Controlled grain size distribution and refinement of an EN AW-6082 aluminium alloy
Authors: Lampke Thomas , Dietrich Dagmar , Nickel Daniela , Bergmann Markus , Zachäus René , Neugebauer Reimund
Published: September 2011

An EN AW-6082 aluminium alloy was subjected to incremental deformation by a new process named gradation rolling. The process has been used to generate a grain size distribution in a rod-shaped billet. A grain size gradient ranging from coarse-grained in the billet core to ultrafine-grained at the surface of the billet can be obtained. The grain size distribution has been confirmed by electron backscatter diffraction showing the grain refinement related to the true strain. The fibre texture of the base material has been transformed to a rolling texture in the surface region. This results in strain-hardening and grain-boundary strengthening in the surface region (130 HV0.5) as compared to the unchanged core material (110 HV0.5).
The effect of layer structure on corrosion and erosion resistance of thin PVD multilayer films
Authors: Depner Udo , Ellermeier Jörg , Troßmann Torsten , Berger Christina , Oechsner Matthias
Published: September 2011

This paper contributes to the development of physical vapour deposition multilayer coatings to resist erosion in corrosive environments. The influence of the deposition parameters of the bonding layer on adhesion has been investigated. Furthermore, the influence of the layer design on the corrosion resistance and the thickness of the diamond-like carbon top layer on the erosion resistance of the investigated multilayer coating have been studied.

Corrosion and erosion tests as well as scratch tests, metallographic and scanning electron microscope investigations were carried out to characterize the coatings and their degradation behaviour.
Microcellular PP vs. Microcellular PP/MMT Nanocomposites: A Comparative Study of Their Mechanical Behavior
Authors: Rizvi S. J. A. , Bhatnagar N.
Published: September 2011

Microcellular foams have attracted interest in both scientific and industrial communities. Injection molding is perhaps the most versatile industrial method of polymer processing. Microcellular injection molding is a newcomer variant in this class. It is capable to produce microcellular structure. The mechanical behavior of a microcellular polymer is different than conventional foams. Although they exhibit much improved mechanical properties than conventional foams still they are inferior to solid polymer. Incorporation of nanoparticles in matrix may affect the nucleation and bubble growth process. Further, nanoparticles will enhance the performance (stiffness, strength etc.) of matrix. In present study an effort has been made to quantitatively analyze the improvements in mechanical properties of microcellular foam with the addition of nanoclay (MMT). Nanocomposite of polypropylene and nanoclay was prepared in a co-rotating twin screw extruder. Maleic anhydride grafted polypropylene (PP-g-MA) was used as compatibilizer. PP/nanocomposites were foamed in a microcellular injection molding machine, where supercritical nitrogen (SCF-N2) was mixed with plasticized PP/nanocomposite inside the screw – barrel assembly. The molded foamed samples were tested for various mechanical properties. Experimental results show that a considerable improvement occur in the property of microcellular polypropylene by the addition of 2 wt.% nanoclay (MMT).
Optimization of Dispersion of Nanosilica Particles in a PP Matrix and Their Effect on Foaming
Authors: Lee S. H. , Zhang Y. , Kontopoulou M. , Park C. B. , Wong A. , Zhai W.
Published: September 2011

Nanocomposites based on isotactic polypropylene (PP) and nanosilica (SiO2) were prepared using a co-rotating twin-screw extruder (TSE). The effect of operating variables, such as screw speed and screw configuration on the dispersion of nanosilica in the polymer matrix has been studied, using TEM imaging. High shear stress, sufficient residence time, and high fill ratio in the melting section of the screw were the most important factors in achieving good nanosilica dispersion. Furthermore, the effects of filler loading and amount of a maleated polypropylene (PP-g-MA) compatibilizer on the degree of SiO2 dispersion were investigated. The foaming performance of the composites was evaluated using a batch foaming simulation system, and an extrusion foaming setup that employed respectively N2 and CO2 blowing agents. Well-dispersed surface-modified hydrophobic SiO2 particles acted as effective nucleating agents for foaming, when used at loadings below 1 phr.
Tsallis Entropy for Geometry Simplification
Authors: Castelló Pascual , González Carlos , Chover Miguel , Sbert Mateu , Feixas Miquel
Published: September 2011

This paper presents a study and a comparison of the use of different information-theoretic measures for polygonal mesh simplification. Generalized measures from Information Theory such as Havrda–Charvát–Tsallis entropy and mutual information have been applied. These measures have been used in the error metric of a surfaces implification algorithm. We demonstrate that these measures are useful for simplifying three-dimensional polygonal meshes. We have also compared these metrics with the error metrics used in a geometry-based method and in an image-driven method. Quantitative results are presented in the comparison using the root-mean-square error (RMSE).
Emergence of Life
Authors: Bassez Marie-Paule
Published: September 2011

Indeed, even if we know that many individual components are necessary for life to exist, we do not yet know what makes life emerge. One goal of this journal Life is to juxtapose articles with multidisciplinary approaches and perhaps to answer in the near future this question of the emergence of life. Different subjects and themes will be developed, starting of course with the multiple definitions of life and continuing with others such as: life diversity and universality; characteristics of living systems; thermodynamics with energy and entropy; kinetics and catalysis; water in its different physical states; circulation of sap and blood and its origin; the first blood pump and first heart; the first exchange of nutrients between cells, sap and blood; essential molecules of living systems; chirality; molecular asymmetry and its origin; formation of enantiomer excess and amplification; microscopic observations on a micrometer and sub-micrometer scales, at molecular and atomic levels; the first molecules at the origin of genetic information, viroids, circular RNA; regions of space or the area inside membranes and cells capable of initiating and maintaining life; phenomena at the origin of the emergence of life; molecules studied in the traditional field of chemistry and in the recent field of nanoscience governed by new laws; interaction between the individual molecules and components of living systems; interaction between living systems and the environment; transfer of information through generations; continuation of life from one generation to the next; prebiotic chemistry and prebiotic signatures on Earth, on Mars, on other planets; biosignatures of the first forms of life; fossils and pseudofossils dating 3.5 Ga ago and more recent ones; experimental fossilization; pluricellular eukaryotes dating 2.1 Ga ago; sudden increase in oxygen in the atmosphere around 2.0 to 2.5 Ga ago and its relation to geology; shell symmetry; aging with transformation of molecules, of their symmetry, their interactions, their exchanges. [...]
Seasonal Dynamics of Microcystis spp. and Their Toxigenicity as Assessed by qPCR in a Temperate Reservoir
Authors: Martins António , Moreira Cristiana , Vale Micaela , Freitas Marisa , Regueiras Ana , Antunes Agostinho , Vasconcelos Vitor
Published: September 2011

Blooms of toxic cyanobacteria are becoming increasingly frequent, mainly due to water quality degradation. This work applied qPCR as a tool for early warning of microcystin(MC)-producer cyanobacteria and risk assessment of water supplies. Specific marker genes for cyanobacteria, Microcystis and MC-producing Microcystis, were quantified to determine the genotypic composition of the natural Microcystis population. Correlations between limnological parameters, pH, water temperature, dissolved oxygen and conductivity and MC concentrations as well as Microcystis abundance were assessed. A negative significant correlation was observed between toxic (with mcy genes) to non-toxic (without mcy genes) genotypes ratio and the overall Microcystis density. The highest proportions of toxic Microcystis genotypes were found 4–6 weeks before and 8–10 weeks after the peak of the bloom, with the lowest being observed at its peak. These results suggest positive selection of non-toxic genotypes under favorable environmental growth conditions. Significant positive correlations could be found between quantity of toxic genotypes and MC concentration, suggesting that the method applied can be useful to predict potential MC toxicity risk. No significant correlation was found between the limnological parameters measured and MC concentrations or toxic genotypes proportions indicating that other abiotic and biotic factors should be governing MC production and toxic genotypes dynamics. The qPCR method here applied is useful to rapidly estimate the potential toxicity of environmental samples and so, it may contribute to the more efficient management of water use in eutrophic systems.
Helichrysum gymnocephalum Essential Oil: Chemical Composition and Cytotoxic, Antimalarial and Antioxidant Activities, Attribution of the Activity Origin by Correlations
Authors: Afoulous Samia , Ferhout Hicham , Raoelison Emmanuel Guy , Valentin Alexis , Moukarzel Béatrice , Couderc François , Bouajila Jalloul
Published: September 2011

Helichrysum gymnocephalum essential oil (EO) was prepared by hydrodistillation of its leaves and characterized by GC-MS and quantified by GC-FID. Twenty three compounds were identified. 1,8-Cineole (47.4%), bicyclosesquiphellandrene (5.6%), γ-curcumene (5.6%), α-amorphene (5.1%) and bicyclogermacrene (5%) were the main components. Our results confirmed the important chemical variability of H. gymnocephalum. The essential oil was tested in vitro for cytotoxic (on human breast cancer cells MCF-7), antimalarial (Plasmodium falciparum: FcB1-Columbia strain, chloroquine-resistant) and antioxidant (ABTS and DPPH assays) activities. H. gymnocephalum EO was found to be active against MCF-7 cells, with an IC50 of 16 ± 2 mg/L. The essential oil was active against P. falciparum (IC50 = 25 ± 1 mg/L). However, the essential oil exhibited a poor antioxidant activity in the DPPH (IC50 value > 1,000 mg/L) and ABTS (IC50 value = 1,487.67 ± 47.70 mg/L) assays. We have reviewed the existing results on the anticancer activity of essential oils on MCF-7 cell line and on their antiplasmodial activity against the P. falciparum. The aim was to establish correlations between the identified compounds and their biological activities (antiplasmodial and anticancer). β-Selinene (R² = 0.76), α-terpinolene (R² = 0.88) and aromadendrene (R² = 0.90) presented a higher relationship with the anti-cancer activity. However, only calamenene (R² = 0.70) showed a significant correlation for the antiplasmodial activity.
Inhibitory Effects of Constituents from Euphorbia lunulata on Differentiation of 3T3-L1 Cells and Nitric Oxide Production in RAW264.7 Cells
Authors: Yang Zhi-Gang , Jia Liu-Nan , Shen Yan , Ohmura Atsuko , Kitanaka Susumu
Published: September 2011

A new flavonol galactopyranoside, myricetin 3-O-(2'',3''-digalloyl)-β-D-galactopyranoide (1), and 23 known constituents, including myricetin 3-O-(2''-galloyl)-β-D-galactopyranoide (2), myricitrin (3), myricetin (4), quercetin 3-O-(2'', 3''-digalloyl)-β-D-galactopyranoide (5), quercetin 3-O-(2''-galloyl)-β-D-galactopyranoide (6), hyperin (7), isoquercetrin (8), quercetin (9), kaempferol (10), apigenin (11), luteolin (12), 3-O-methylquercetin (13), 5,7,2',5'-tetrahydroxyflavone (14), 1,3,4,6-tetra-O-galloyl-β-D-glucose (15), 1,2,6-tri-O-galloyl-β-D-glucose (16), 1,3,6-tri-O-galloyl-β-D-glucose (17), gallic acid (18), protocatechuic acid (19), 3,4,5-trimethoxybenzoic acid (20), 2,6-dihydroxyacetophenone (21), 3,3'-di-O-methylellagic acid (22), ellagic acid (23) and esculetin (24) were isolated from Euphorbia lunulata Bge. Their structures were determined by spectroscopic analysis. Isolated hydrolysable tannins, flavonoids, and flavonol galactopyranoside gallates showed significant inhibition of the differentiation of 3T3-L1 preadipocytes and triglyceride accumulation in maturing adipocytes, and nitric oxide production in RAW 264.7 cells.
Role of Kupffer Cells in Thioacetamide-Induced Cell Cycle Dysfunction
Authors: Bautista Mirandeli , Andres David , Cascales María , Morales-González José A. , Sánchez-Reus María Isabel , Madrigal-Santillán Eduardo , Valadez-Vega Carmen , Fregoso-Aguilar Tomas , Mendoza-Pérez Jorge Alberto , Gutiérrez-Salinas José , Esquivel-Soto Jaime
Published: September 2011

It is well known that gadolinium chloride (GD) attenuates drug-induced hepatotoxicity by selectively inactivating Kupffer cells. In the present study the effect of GD in reference to cell cycle and postnecrotic liver regeneration induced by thioacetamide (TA) in rats was studied. Two months male rats, intraveously pretreated with a single dose of GD (0.1 mmol/Kg), were intraperitoneally injected with TA (6.6 mmol/Kg). Samples of blood and liver were obtained from rats at 0, 12, 24, 48, 72 and 96 h following TA intoxication. Parameters related to liver damage were determined in blood. In order to evaluate the mechanisms involved in the post-necrotic regenerative state, the levels of cyclin D and cyclin E as well as protein p27 and Proliferating Cell Nuclear Antigen (PCNA) were determined in liver extracts because of their roles in the control of cell cycle check-points. The results showed that GD significantly reduced the extent of necrosis. Noticeable changes were detected in the levels of cyclin D1, cyclin E, p27 and PCNA when compared to those induced by thioacetamide. Thus GD pre-treatment reduced TA-induced liver injury and accelerated the postnecrotic liver regeneration. These results demonstrate that Kupffer cells are involved in TA-induced liver and also in the postnecrotic proliferative liver states.
Determination of Ammonium Ion Using a Reagentless Amperometric Biosensor Based on Immobilized Alanine Dehydrogenase
Authors: Tan Ling Ling , Musa Ahmad , Lee Yook Heng
Published: September 2011

The use of the enzyme alanine dehydrogenase (AlaDH) for the determination of ammonium ion (NH4+) usually requires the addition of pyruvate substrate and reduced nicotinamide adenine dinucleotide (NADH) simultaneously to effect the reaction. This addition of reagents is inconvenient when an enzyme biosensor based on AlaDH is used. To resolve the problem, a novel reagentless amperometric biosensor using a stacked methacrylic membrane system coated onto a screen-printed carbon paste electrode (SPE) for NH4+ ion determination is described. A mixture of pyruvate and NADH was immobilized in low molecular weight poly(2-hydroxyethyl methacrylate) (pHEMA) membrane, which was then deposited over a photocured pHEMA membrane (photoHEMA) containing alanine dehydrogenase (AlaDH) enzyme. Due to the enzymatic reaction of AlaDH and the pyruvate substrate, NH4+ was consumed in the process and thus the signal from the electrocatalytic oxidation of NADH at an applied potential of +0.55 V was proportional to the NH4+ ion concentration under optimal conditions. The stacked methacrylate membranes responded rapidly and linearly to changes in NH4+ ion concentrations between 10–100 mM, with a detection limit of 0.18 mM NH4+ ion. The reproducibility of the amperometrical NH4+ biosensor yielded low relative standard deviations between 1.4–4.9%. The stacked membrane biosensor has been successfully applied to the determination of NH4+ ion in spiked river water samples without pretreatment. A good correlation was found between the analytical results for NH4+ obtained from the biosensor and the Nessler spectrophotometric method.
Oral Anti-Cancer Agents in the Community Setting: A Survey of Pharmacists in Newfoundland and Labrador
Authors: Abbott Rick , Edwards Scott , Edwards Jonathan , Dranitsaris George , McCarthy Joy
Published: September 2011

Background:

Over the past decade, there has been a sharp rise in the approval of orally administered anti-cancer agents for disease control. The increase in the use of oral anti-cancer agents (OAAs) raises concerns that community pharmacists may not have the training to safely dispense these agents and provide effective patient care. In order to identify the needs of community pharmacists with respect to oral anti-cancer therapy, a survey was conducted in the province of Newfoundland and Labrador.

Methods:

A structured electronic mailing strategy was used. Standardized data collection forms with a cover letter were electronically mailed to 560 practising pharmacists. Survey items included questions related to demographic information, practice setting, current knowledge related to cancer therapy, education needs, access to resources, patient education, patient and pharmacist safety and required elements of an OAA prescription.

Results:

The response rate was 39%. Only 9.6% of respondents felt that they had received adequate oncology education at the undergraduate level and approximately 31% had attended a continuing education event related to oncology in the past 2 years. Just 17% of respondents stated that they used protective equipment when dispensing OAAs. Only 28% of the pharmacists who responded were familiar with the common doses of OAAs and approximately 25% felt comfortable educating patients on these medications.

Conclusions:

A substantial portion of community pharmacists in Newfoundland and Labrador do not have a solid understanding of oral anti-cancer therapy. These educational gaps must be addressed to ensure patient safety as well as the safe handling and dispensing of OAAs by community pharmacists.
Pharmacy Faculty Members' Perception of Contemporary Pharmacy Practice
Authors: Ng Karen W.K. , Rosenthal Meagen M. , Tsuyuki Ross T.
Published: September 2011

Objective:

Previous research has shown that community pharmacists describe their role mostly in product-focused rather than patient-centred terms. We wondered if pharmacy faculty members think similarly, which might influence how students, and subsequently, new pharmacists think. The objective of this study was to examine how pharmacy faculty members describe the health care role of pharmacists.

Method:

We telephoned 101 randomly selected Canadian pharmacy faculty members. The surveyor posed as a sociology student studying the use of language. We asked a single question: “What does a pharmacist do?,” asking respondents to answer in a few short phrases that were recorded verbatim. Responses were analyzed by content and categories were established from previous studies, coded as “patient-centred,” “product-focused (dispensing),” “research” or “business-related.”

Results:

Ninety-four faculty members (71% were pharmacists) provided 200 responses. Of the responses, 40% were categorized as patient-centred, 32.5% were product-focused and 5% were research- or business-related. Evaluating participants' first responses, faculty members who were pharmacists offered a patient-centred description in 59% of responses, while non-pharmacists provided a more pro duct-focused description. The most frequently used terms to describe a pharmacist's role were: patient, medication, educate, dispense, responsible, safety and ensure.

Conclusions:

Pharmacy faculty members' perception of the role of pharmacists may influence the culture of the profession. We found that faculty members were more idealistic about patient-centred roles for pharmacists than community or hospital pharmacists, but a large proportion (mainly nonpharmacist faculty members) still describe a product-focused role.
Pharmacokinetics of Antiretroviral Drugs in Anatomical Sanctuary Sites: The Fetal Compartment (Placenta and Amniotic Fluid)
Authors: Else Laura J , Taylor Stephen , Back David J , Khoo Saye H
Published: September 2011

HIV resides within anatomical ‘sanctuary sites’ where local drug exposure and viral dynamics may differ significantly from the systemic compartment. Widespread implementation of antiretroviral therapy has seen a significant decline in the incidence of mother-to-child transmission (MTCT) of HIV. In addition to suppression of maternal plasma/genital viral loads, antiretroviral agents that cross the placenta and achieve adequate concentrations in the fetal compartment may exert a greater prophylactic effect.

Penetration of antiretrovirals in the fetal compartment is expressed by accumulation ratios derived from the measurement of drug concentrations in paired maternal plasma and umbilical cord samples. The nucleoside analogues and nevirapine accumulate extensively in cord blood and in the surrounding amniotic fluid, whereas the protease inhibitors (PIs) exhibit low-to-moderate placental accumulation. Early data suggest that high placental/neonatal concentrations are achieved with raltegravir, but to a lesser extent with etravirine and maraviroc (rank order of accumulation: raltegravir/nucleoside reverse transcriptase inhibitor [tenofovir > zidovudine/lamivudine/emtricitabine/stavudine/abacavir] > non-nucleoside reverse transcriptase inhibitor [nevirapine > etravirine] > PI > maraviroc/enfuvirtide). More comprehensive in vivo pharmacokinetic data are required to justify the potential use of these agents as safe and effective options during pregnancy.
Effect of different icing conditions on lipid damage development in chilled horse mackerel (Trachurus trachurus) muscle
Authors: Sanjuás-Rey M. , Barros-Velázquez J. , Aubourg S. P.
Published: September 2011

This study was aimed at investigating the effect of including a mixture of natural organic acids (citric, ascorbic and lactic) in the icing medium employed during the chilled storage of horse mackerel (Trachurus trachurus). To this end, two aqueous solutions including 0.005% and 0.020% (w/v) of each acid (P-1 and P-2 conditions, respectively) were employed as icing systems. The effects on lipid damage development in fish muscle were monitored for up to a 13- day storage period; complementary chemical quality and sensory acceptance analyses were carried out. According to peroxide and thiobarbituric acid reactive substance assessment, a slight inhibitory effect was concluded as a result of the acid mixture present in the chilling medium. At the same time, P-2-treated fish showed a longer shelf life than their counterparts belonging to P-1 and control conditions. No effect of the acid presence in the icing system could be outlined on the nucleotide degradation or the free fatty acid formation.
Traditional process of green table olives. Rationalization of alkaline treatment
Authors: Jaramillo Carmona S. , De Castro A. , Rejano Navarro L.
Published: September 2011

In order for olives of the Manzanilla variety to be produced as Spanish-style, they require a previous storage period before their alkaline treatment with NaOH. This holding time prevents the breakage and shedding of the fruit epidermis, but at the same time, causes an increase in the number of olives with surface blemishes and, consequently, loss in product quality. The objectives of this work were to investigate, at industrial scale, different alternatives to the holding period; specifically, the use of low-concentration alkaline solutions before the real alkaline treatment, and the use of alkaline solutions at low temperatures for this alkaline treatment. Basic parameters of the fermentative processes carried out in every treatment were monitored, and commercial quality of the final product was ascertained. The results indicate that both modifications are alternatives to the traditional treatment, and the products obtained applying these modifications have the same or higher quality than those obtained by the traditional process.
Effects of convective and microwave roasting on the physicochemical properties of cocoa beans and cocoa butter extracted from this material
Authors: Krysiak W.
Published: September 2011

The cocoa beans of the Ivory Coast variety were convectively and microwave roasted. The effects of roasting conditions on the principal physicochemical attributes (water and fat contents, total and volatile acidity) of roasted cocoa beans and the properties of fat extracted from this material (acidity, saponification index, iodine index, peroxide value, light refraction coefficient, polar fraction content, and Fatty Acid profile, absorbancy of 1 and 10% solution in hexane) were examined. The characteristics of roasted and raw cocoa beans and their lipid fractions were compared. Results of analyses showed that convective roasting for 35 min at 135°C, air flow rate 1.0mxs-1 and relative humidity RH of 0.45% caused the least advanced changes in fat quality while microwave roasting promoted oxidation of lipids although the quality of roasted cocoa beans was the best.
Ouverture du colloque « La cour et les sciences : naissance des politiques scientifiques dans les cours européennes aux xviie et xviiie siècles »
Authors: Aillagon Jean-Jacques , Saule Béatrix
Published: September 2011

À l’occasion de l’exposition « Sciences et curiosités à la cour de Versailles » au château de Versailles (26 octobre 2010 au 3 avril 2011), le Centre de recherche du château de Versailles a organisé le colloque « La cour et les sciences : naissance des politiques scientifiques dans les cours européennes aux xviie et xviiie siècles ». Pour les sciences et pour le royaume – devrions-nous dire. En effet, la cour, siège du pouvoir et lieu de concentration des capitaux, soutenait la recherche scientifique tandis que cette dernière devait servir les intérêts généraux du pays et la gloire de son souverain. En un temps qui ignorait encore la séparation entre les deux cultures, scientifique et technique d’un côté, humaniste et artistique de l’autre, on vit cependant s’affirmer une nouvelle idée de la science. Cette modernité, la plupart du temps, ne put exister sans le concours actif des princes. La cour, comme lieu d’expérimentation, d’innovations techniques, apparaît comme un des moteurs des évolutions de la recherche, permettant notamment des applications concrètes. L’implication des souverains européens, par leur éducation, par leurs rapports privilégiés avec les savants, fut souvent à l’origine du développement des connaissances scientifiques dans de nombreux domaines. Dans ce colloque, il s’agit donc essentiellement d’étudier les politiques scientifiques volontaristes ou non des états européens sous l’Ancien Régime en s’attachant particulièrement à la recherche « fondamentale » et à la recherche « utile » (amélioration de la santé, lutte contre la famine, progrès des techniques, des constructions et des bâtiments, etc.). Volontairement comparatistes, les études englobent l’aire géographique européenne à travers trois axes : le financement des sciences et des scientifiques, la communauté scientifique face à la cour et, enfin, la diffusion et la culture scientifique à la cour.
Critical Roles of ASC Inflammasomes in Caspase-1 Activation and Host Innate Resistance to Streptococcus pneumoniae Infection
Authors: Fang Rendong , Tsuchiya Kohsuke , Kawamura Ikuo , Shen Yanna , Hara Hideki , Sakai Shunsuke , Yamamoto Takeshi , Fernandes-Alnemri Teresa , Yang Ruili , Hernandez-Cuellar Eduardo , Dewamitta Sita R. , Xu Yanting , Qu Huixin , Alnemri Emad S. , Mitsuyama Masao
Published: September 2011

Streptococcus pneumoniae is a Gram-positive, extracellular bacterium that is responsible for significant mortality and morbidity worldwide. Pneumolysin (PLY), a cytolysin produced by all clinical isolates of the pneumococcus, is one of the most important virulence factors of this pathogen. We have previously reported that PLY is an essential factor for activation of caspase-1 and consequent secretion of IL-1β and IL-18 in macrophages infected with S. pneumoniae. However, the host molecular factors involved in caspase-1 activation are still unclear. To further elucidate the mechanism of caspase-1 activation in macrophages infected with S. pneumoniae, we examined the involvement of inflammasomes in inducing this cellular response. Our study revealed that apoptosis-associated specklike protein containing a caspase recruitment domain (ASC), an adaptor protein for inflammasome receptors such as nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2), is essentially required for the induction of caspase-1 activation by S. pneumoniae. Caspase-1 activation was partially impaired in NLRP3−/− macrophages, whereas knockdown and knockout of AIM2 resulted in a clear decrease in caspase-1 activation in response to S. pneumoniae. These results suggest that ASC inflammasomes, including AIM2 and NLRP3, are critical for caspase-1 activation induced by S. pneumoniae. Furthermore, ASC−/− mice were more susceptible than wild-type mice to S. pneumoniae, with impaired secretion of IL-1β and IL-18 into the bronchoalveolar lavage after intranasal infection, suggesting that ASC inflammasomes contribute to the protection of host from infection with PLY-producing S. pneumoniae.
Pyridone 6, a Pan-JAK Inhibitor, Ameliorates Allergic Skin Inflammation of NC/Nga Mice via Suppression of Th2 and Enhancement of Th17
Authors: Nakagawa Ryusuke , Yoshida Hideyuki , Asakawa Mayako , Tamiya Taiga , Inoue Naoko , Morita Rimpei , Inoue Hiromasa , Nakao Atsuhito , Yoshimura Akihiko
Published: September 2011

Atopic dermatitis (AD) is a common pruritic inflammatory disease triggered by a defective skin barrier and immunodysregulation. AD has been considered a typical example of a Th2 response associated with allergic disease. In the early phases of the disease, symptoms include IgE hyperproduction, eosinophil accumulation, and mast cell activation; in the chronic phase, a Th1-dominant immune response is also observed at the sites of AD skin lesions. The role of IL-17–producing Th (Th17) cells in AD has not been established. In the current study, we found that pyridone 6 (P6), a pan-JAK inhibitor, delayed the onset and reduced the magnitude of skin disease in an AD-like skin-disease model of NC/Nga mice. P6 reduced IFN-γ and IL-13, whereas it enhanced IL-17 and IL-22 expression. In vitro, P6 also inhibited both Th1 and Th2 development, whereas it promoted Th17 differentiation from naive T cells when present within a certain range of concentrations. This was probably because P6 strongly inhibited STAT1, STAT5, and STAT6 phosphorylation, whereas STAT3 phosphorylation was less efficiently suppressed by P6 at the same concentration. Furthermore, IL-22 protects keratinocytes from apoptosis induced by IFN-γ, and administration of IL-17 and IL-22 partially ameliorated skin diseases in NC/Nga mice. These results suggested that the JAK inhibitor P6 is therapeutic for AD by modulating the balance of Th2 and Th17.
Hepatitis B Virus Induces a Novel Inflammation Network Involving Three Inflammatory Factors, IL-29, IL-8, and Cyclooxygenase-2
Authors: Yu Yi , Gong Rui , Mu Yongxin , Chen Yanni , Zhu Chengliang , Sun Zhichen , Chen Mingzhou , Liu Yingle , Zhu Ying , Wu Jianguo
Published: September 2011

Chronic inflammation induced by hepatitis B virus (HBV) is a major causative factor associated with the development of cirrhosis and hepatocellular carcinoma. In this study, we investigated the roles of three inflammatory factors, IL-8, IL-29 (or IFN-λ1), and cyclooxygenase-2 (COX-2), in HBV infection. We showed that the expression of IL-29, IL-8, and COX-2 genes was enhanced in HBV-infected patients or in HBV-expressing cells. In HBV-transfected human lymphocytes and hepatocytes, IL-29 activates the production of IL-8, which in turn enhances the expression of COX-2. In addition, COX-2 decreases the production of IL-8, which in turn attenuates the expression of IL-29. Thus, we proposed that HBV infection induces a novel inflammation cytokine network involving three inflammatory factors that regulate each other in the order IL-29/IL-8/COX-2, which involves positive regulation and negative feedback. In addition, we also demonstrated that COX-2 expression activated by IL-8 was mediated through CREB and C/EBP, which maintains the inflammatory environment associated with HBV infection. Finally, we showed that the ERK and the JNK signaling pathways were cooperatively involved in the regulation of COX-2. We also demonstrated that IL-29 inhibits HBV replication and that IL-8 attenuates the expression of IL-10R2 and the anti-HBV activity of IL-29, which favors the establishment of persistent viral infection. These new findings provide insights for our understanding of the mechanism by which inflammatory factors regulate each other in response to HBV infection.
DHX9 Pairs with IPS-1 To Sense Double-Stranded RNA in Myeloid Dendritic Cells
Authors: Zhang Zhiqiang , Yuan Bin , Lu Ning , Facchinetti Valeria , Liu Yong-Jun
Published: September 2011

The innate immune system is equipped with many molecular sensors for microbial DNA/RNA to quickly mount antimicrobial host immune responses. In this paper, we identified DHX9, a DExDc helicase family member, as an important viral dsRNA sensor in myeloid dendritic cells (mDCs). Knockdown of DHX9 expression by small heteroduplex RNA dramatically blocked the ability of mDCs to produce IFN-α/β and proinflammatory cytokines in response to polyinosine-polycytidylic acid, influenza A, and reovirus. DHX9 could specifically bind polyinosine-polycytidylic acid via its double-strand RNA binding motifs. DHX9 interacted with IPS-1 via the HelicC-HA2-DUF and CARD domains of DHX9 and IPS-1, respectively. Knockdown of DHX9 expression in mDCs blocked the activation of NF-κB and IFN regulatory factor 3 by dsRNA. Collectively, these results suggest that DHX9 is an important RNA sensor that is dependent on IPS-1 to sense pathogenic RNA.
Mycobacterial Secretion Systems ESX-1 and ESX-5 Play Distinct Roles in Host Cell Death and Inflammasome Activation
Authors: Abdallah Abdallah M. , Bestebroer Jovanka , Savage Nigel D. L. , de Punder Karin , van Zon Maaike , Wilson Louis , Korbee Cees J. , van der Sar Astrid M. , Ottenhoff Tom H. M. , van der Wel Nicole N. , Bitter Wilbert , Peters Peter J.
Published: September 2011

During infection of humans and animals, pathogenic mycobacteria manipulate the host cell causing severe diseases such as tuberculosis and leprosy. To understand the basis of mycobacterial pathogenicity, it is crucial to identify the molecular virulence mechanisms. In this study, we address the contribution of ESX-1 and ESX-5—two homologous type VII secretion systems of mycobacteria that secrete distinct sets of immune modulators—during the macrophage infection cycle. Using wild-type, ESX-1– and ESX-5–deficient mycobacterial strains, we demonstrate that these secretion systems differentially affect subcellular localization and macrophage cell responses. We show that in contrast to ESX-1, the effector proteins secreted by ESX-5 are not required for the translocation of Mycobacterium tuberculosis or Mycobacterium marinum to the cytosol of host cells. However, the M. marinum ESX-5 mutant does not induce inflammasome activation and IL-1β activation. The ESX-5 system also induces a caspase-independent cell death after translocation has taken place. Importantly, by means of inhibitory agents and small interfering RNA experiments, we reveal that cathepsin B is involved in both the induction of cell death and inflammasome activation upon infection with wild-type mycobacteria. These results reveal distinct roles for two different type VII secretion systems during infection and shed light on how virulent mycobacteria manipulate the host cell in various ways to replicate and spread.
Mechanism for Pre-B Cell Loss in VH-Mutant Rabbits
Authors: Robbins Gregory R. , Knight Katherine L.
Published: September 2011

Pre-BCR signaling is a critical checkpoint in B cell development in which B-lineage cells expressing functional IgH μ-chain are selectively expanded. B cell development is delayed in mutant ali/ali rabbits because the a-allotype encoding VH1 gene, which is normally used in VDJ gene rearrangements in wt rabbits, is deleted, and instead, most B-lineage cells use the a-allotype encoding VH4 gene [VH4(a)], which results in a severe developmental block at the pre-B cell stage. We found that VH4(a)-utilizing pre-B cells exhibit reduced pre-BCR signaling and do not undergo normal expansion in vitro. Transduction of murine 38B9 pre-B cells with chimeric rabbit-VDJ mouse-Cμ encoding retroviruses showed VH4(a)-encoded μ-chains do not readily form signal-competent pre-BCR, thereby explaining the reduction in pre-BCR signaling and pre-B cell expansion. Development of VH4(a)-utilizing B cells can be rescued in vivo by the expression of an Igκ transgene, indicating that VH4(a)-μ chains are not defective for conventional BCR formation and signaling. The ali/ali rabbit model system is unique because VH4(a)-μ chains have the capacity to pair with a variety of conventional IgL chains and yet lack the capacity to form a signal-competent pre-BCR. This system could allow for identification of critical structural parameters that govern pre-BCR formation/signaling.
HIV-1N-Glycan Composition Governs a Balance between Dendritic Cell-Mediated Viral Transmission and Antigen Presentation
Authors: van Montfort Thijs , Eggink Dirk , Boot Maikel , Tuen Michael , Hioe Catarina E. , Berkhout Ben , Sanders Rogier W.
Published: September 2011

The natural function of dendritic cells (DCs) is to capture and degrade pathogens for Ag presentation. However, HIV-1 can evade viral degradation by DCs and hijack DCs for migration to susceptible CD4+ T lymphocytes. It is unknown what factors decide whether a virus is degraded or transmitted to T cells. The interaction of DCs with HIV-1 involves C-type lectin receptors, such as DC-specific ICAM-3–grabbing nonintegrin, which bind to the envelope glycoprotein complex (Env), which is decorated heavily with N-linked glycans. We hypothesized that the saccharide composition of the Env N-glycans is involved in avoiding viral degradation and Ag presentation, as well as preserving infectious virus for the transmission to target cells. Therefore, we studied the fate of normally glycosylated virus versus oligomannose-enriched virus in DCs. Changing the heterogeneous N-linked glycan composition of Env to uniform oligomannose N-glycans increased the affinity of HIV-1 for DC-specific ICAM-3–grabbing nonintegrin and enhanced the capture of HIV-1 by immature DCs; however, it decreased the subsequent transmission to target cells. Oligomannose-enriched HIV-1 was directed more efficiently into the endocytic pathway, resulting in enhanced viral degradation and reduced virus transfer to target cells. Furthermore, Env containing exclusively oligomannose N-glycans was presented to Env-specific CD4+ T cells more efficiently. Taken together, our results showed that the HIV-1 N-glycan composition plays a crucial role in the balance between DC-mediated Ag degradation and presentation and DC-mediated virus transmission to target cells. This finding may have implications for the early events in HIV-1 transmission and the induction of antiviral immune responses.
Isolation, Purification, and Characterization of Fungal Laccase from Pleurotus sp.
Authors: More Sunil S. , P. S. Renuka , K. Pruthvi , M. Swetha , Malini S. , S. M. Veena
Published: September 2011

Laccases are blue copper oxidases (E.C. 1.10.3.2 benzenediol: oxygen oxidoreductase) that catalyze the one-electron oxidation of phenolics, aromatic amines, and other electron-rich substrates with the concomitant reduction of O2 to H2O. They are currently seen as highly interesting industrial enzymes because of their broad substrate specificity. A positive strain was isolated and characterized as nonspore forming Basidiomycetes Pleurotus sp. Laccase activity was determined using ABTS as substrate. Laccase was purified by ionexchange and gel filtration chromatography. The purified laccase was a monomer showed a molecular mass of 40±1 kDa as estimated by SDS-PAGE and a 72-fold purification with a 22% yield. The optimal pH and temperature were 4.5 and 65°C, respectively. The Km and Vmax⁡ values are 250 (mM) and 0.33 (μmol/min), respectively, for ABTS as substrate. Metal ions like CuSO4, BaCl2, MgCl2, FeCl2, ZnCl2 have no effect on purified laccase whereas HgCl2 and MnCl2 moderately decrease enzyme activity. SDS and sodium azide inhibited enzyme activity, whereas Urea, PCMB, DTT, and mercaptoethanol have no effect on enzyme activity. The isolated laccase can be used in development of biosensor for detecting the phenolic compounds from the effluents of paper industries.
Spot-On Skin Lipid Complex as an Adjunct Therapy in Dogs with Atopic Dermatitis: An Open Pilot Study
Authors: Fujimura Masato , Nakatsuji Yoshinobu , Fujiwara Subaru , Rème Christophe , Gatto Hugues
Published: September 2011

The purpose of this paper was to evaluate the efficacy of topical skin lipid complex (SLC) in canine atopic dermatitis (AD). Eight dogs with chronic AD and no improvement of main therapy in symptoms, erythema, lichenification, excoriation, and alopecia in the previous month were treated with SLC topically as adjunct therapy at lesion sites twice weekly for 12 weeks. A statistically significant reduction (26.0%, ) in the third version of the Canine Atopic Dermatitis Extent and Severity Index (CADESI-03) modification from baseline was recorded 6 weeks after treatment, with marked reduction in the erythema subscore (36.2%, ). A significant reduction in excoriation and alopecia subscores was observed 6 weeks after treatment (39.9%, and 19.9%, , resp.). However, the lichenification subscore was not reduced significantly at 6 or 12 weeks. These findings suggest that topical SLC may have therapeutic and clinical benefits in dogs with AD.
Optical Coherence Tomography Imaging in Acute Coronary Syndromes
Authors: Kubo Takashi , Ino Yasushi , Tanimoto Takashi , Kitabata Hironori , Tanaka Atsushi , Akasaka Takashi
Published: September 2011

Optical coherence tomography (OCT) is a high-resolution imaging technique that offers microscopic visualization of coronary plaques. The clear and detailed images of OCT generate an intense interest in adopting this technique for both clinical and research purposes. Recent studies have shown that OCT is useful for the assessment of coronary atherosclerotic plaques, in particular the assessment of plaque rupture, erosion, and intracoronary thrombus in patients with acute coronary syndrome. In addition, OCT may enable identifying thin-cap fibroatheroma, the proliferation of vasa vasorum, and the distribution of macrophages surrounding vulnerable plaques. With its ability to view atherosclerotic lesions in vivo with such high resolution, OCT provides cardiologists with the tool they need to better understand the thrombosis-prone vulnerable plaques and acute coronary syndromes. This paper reviews the possibility of OCT for identification of vulnerable plaques in vivo.
Nuclear Reprogramming in Mouse Primordial Germ Cells: Epigenetic Contribution
Authors: De Felici Massimo
Published: September 2011

The unique capability of germ cells to give rise to a new organism, allowing the transmission of primary genetic information from generation to generation, depends on their epigenetic reprogramming ability and underlying genomic totipotency. Recent studies have shown that genome-wide epigenetic modifications, referred to as “epigenetic reprogramming”, occur during the development of the gamete precursors termed primordial germ cells (PGCs) in the embryo. This reprogramming is likely to be critical for the germ line development itself and necessary to erase the parental imprinting and setting the base for totipotency intrinsic to this cell lineage. The status of genome acquired during reprogramming and the associated expression of key pluripotency genes render PGCs susceptible to transform into pluripotent stem cells. This may occurin vivounder still undefined condition, and it is likely at the origin of the formation of germ cell tumors. The phenomenon appears to be reproduced under partly definedin vitroculture conditions, when PGCs are transformed into embryonic germ (EG) cells. In the present paper, I will try to summarize the contribution that epigenetic modifications give to nuclear reprogramming in mouse PGCs.
Lambert-Eaton Myasthenic Syndrome; Pathogenesis, Diagnosis, and Therapy
Authors: Gilhus Nils Erik
Published: September 2011

Lambert-Eaton Myasthenic Syndrome (LEMS) is a rare disease with a well-characterized pathogenesis. In 50% of the patients, LEMS is a paraneoplastic manifestation and caused by a small cell lung carcinoma (SCLC). Both LEMS patients with SCLC and those without this tumour have in 85% of cases pathogenetic antibodies of very high LEMS specificity against voltage-gated calcium channels (VGCCs) in the cell membrane of the presynaptic motor nerve terminal. Better understanding of LEMS pathogenesis has lead to targeted symptomatic therapy aimed at the neuromuscular junction and to semispecific immuno-suppression. For SCLC LEMS, tumour therapy is essential.