bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydroelectric power: present role and future prospects
Authors: Bartle Alison , Hallowes George
Published: October 2005

Hydropower currently provides around 19% of the world's supply of electricity, but only 1·5% in the UK. This paper argues that although hydropower will never be sufficient alone to meet increasing world needs for electricity, it is a clean renewable source of energy that should be exploited to the maximum possible extent. It reports that significant potential exists for both development of new hydro schemes and the uprating, at relatively low cost, of existing ones. The greatest potential is available in developing countries but there is scope for substantial development in many parts of Europe, where only 45% of the resource has been exploited. In the UK, more small hydro could be developed and more pumped storage schemes may be required to balance increasing investment in wind and tidal power.
Marine energy: getting power from tides and waves
Authors: Kerr David
Published: October 2005

Marine renewable energy has the potential to make a significant contribution to energy supplies in the future. Tidal barrages and wave energy could make the largest contribution, both in the UK and elsewhere, and tidal streams could make a smaller but still useful contribution. This paper provides an overview of the current status and prospects for electrical generation from marine energy. It concludes that a realistic target contribution to UK electricity supplies would be about 75 TWh. However, although tidal power is predictable, all forms of marine energy are variable and intermittent and integration into the electrical grid is a critical issue if they are to achieve their potential contribution.
UK power: an everchanging challenge for civil engineers
Authors: Price Anthony
Published: October 2005

This paper provides an overview of Britain's continually evolving electricity supply industry and how it got to where it is today. In an ever-changing social, political and technical environment, the industry has gone from private to public ownership and back again, and the benefits of a partial return to distributed generation are now becoming apparent. Continually rising demand and an increased emphasis on sustainability and security are now leading to further restructuring. All of this continues to supply a rich variety of challenges and opportunities for civil engineers, whose role in developing, upgrading and maintaining the nation's power-system infrastructure remains as vital as ever.
Geothermal energy: a major renewable energy resource
Authors: Batchelor Tony
Published: October 2005

Geothermal energy—which covers all forms of heat extracted from the earth—has been used on a commercial scale for over 100 years. The resource is available in one form or another in every country and can provide base-load electricity and heat on a continuous and sustained basis. More than 70 countries now exploit geothermal resources, the global scale of which means they do not suffer depletion in the same way as more finite mineral resources. This paper reviews the various forms of geothermal energy production currently in operation and planned around the world. It concludes that geothermal energy has potential for further substantial growth and can make a large contribution to reduction of greenhouse gas emissions, particularly in developing countries.
Electrical energy storage—a review of technology options
Authors: Price Anthony
Published: October 2005

Matching uneven generation patterns to varying demands for power requires flexibility in the power network. Electrical energy storage technologies now exist to complement mature generation types as well as new forms of renewable generation. Electrical energy storage can also support network management. This paper presents examples of electrical energy storage applications, together with the development status of several technologies, and introduces the regulatory, economic and commercial aspects of combining storage with sustainable generation and operation of grid-connected and standalone power networks.
Nuclear fusion power: a bright long-term future
Authors: Llewellyn Smith Chris , Ward David
Published: October 2005

Nuclear fusion, the process that powers the sun and stars, could be a viable commercial power source within 40 years. The Joint European Torus, the world's leading fusion facility in the UK, has produced 16 MW of fusion power. Fusion produces relatively very little waste, is intrinsically safe and has essentially limitless supplies of fuel. There has been substantial progress in recent decades, although significant challenges remain. This paper summarises the basics of nuclear fusion, describes the present state of technology development and outlines the remaining steps needed to develop fusion power as a commercial reality.
The rise and fall of Edinburgh's congestion charging plans
Authors: Saunders J. P. F.
Published: October 2005

A referendum in February 2005 saw Edinburgh citizens reject a transport strategy for the city, including a proposed congestion charging scheme. The aims of the strategy were to tackle road congestion and to provide a public transport system to match the best in Europe. Congestion charging was seen by the Council as a key tool both to reduce demand for road space and to provide a revenue stream for transport investment. This paper focuses on the context for the development of the proposals, the hurdles involved in taking them forward, and the apparent contradiction between initial high levels of support for a ‘radical’ transport policy and eventual rejection of the proposed means of achieving those objectives. The paper postulates a number of reasons why this rejection may have occurred, based on the author's experience in the development of the scheme.
Stochastic model for strategic assessment of road maintenance
Authors: Costello S. B. , Snaith M. S. , Kerali H. G. R. , Tachtsi L. V. , Ortiz-García J. J.
Published: October 2005

This paper describes the development of a stochastic model for the strategic assessment of road maintenance funding and policy decisions. The algorithms used for simulating pavement deterioration utilise Markov processes, resulting in a transition probability matrix that defines defect progression as opposed to the more familiar regression-type model popular with engineers. The model is designed to be used by road maintenance managers and senior administrators for planning medium- to long-term maintenance investment requirements for local and national road networks. Finally, the application of the model is demonstrated with a case study from central Europe.
Using graphical models to interpret pavement condition data
Authors: Attoh-Okine N. O. , Paris D.
Published: October 2005

Most of the multiple linear regressions developed in pavement performance studies have one response variable and one block of several explanatory variables. In this paper, graphical chain models are used to develop blocks of several possibly interacting responses with each block containing several interacting variables. The graphical chain model provides easy interpretation of conditional independence structure within the blocks. This ultimately provides an idea about association and dependence of different pavement condition variables. An example was presented using data from the Highway maintenance and Design Model (HDM).
Enhanced Hole Mobility in Regioregular Polythiophene Infiltrated in Straight Nanopores
Authors: Coakley K. M. , Srinivasan B. S. , Ziebarth J. M. , Goh C. , Liu Y. , McGehee M. D.
Published: October 2005

We demonstrate that the hole mobility in regioregular poly(3‐hexylthiophene) can be enhanced by a factor of 20 by infiltrating it into straight nanopores of anodic alumina. Optical characterization shows that the polymer chains are partially aligned in the charge‐transport direction.
SPME Sampling of BTEX before GC/MS Analysis: Examples of outdoor and indoor Air Quality Measurements in Public and Private Sites
Authors: Tumbiolo Simonetta , Gal Jean‐François , Maria Pierre‐Charles , Zerbinati Orfeo
Published: October 2005

This article presents the results of an exploratory application of the Solid Phase MicroExtraction (SPME) technique to the analysis of BTEX (benzene, toluene, ethylbenzene and xylenes) at the μg/m3 level in outdoor and indoor air. The salient features of the method validation are reported. As shown by the various examples of field sampling described, SPME technique appears as a method of choice for fast qualitative analysis and quantitative determination of Volatile Organic Compounds (VOC). The small dimensions of the SPME sampling system and the short sampling time let envisage its utilisation for the rapid diagnostic of outdoor and indoor air quality.
Evaluation of Mutual Connections between Zero‐Valent Iron Reactivity and Groundwater Composition in Trichloroethylene Degradation
Authors: Zanetti Maria Chiara , Fiore Silvia
Published: October 2005

Zero‐valent iron Permeable Reactive Barriers (PRBs) are an efficient and relatively low cost in situ technology for the remediation of aquifers polluted by chlorinated solvents. The groundwater composition and the zero‐valent iron reactive material are linked by mutual connections. The groundwater, to a certain extent depending on its composition, is able to oxidize the metallic iron, thus decreasing its reactivity; on the other hand, the dechlorination process and the leaching of chemical species from the reactive substrate may deeply modify groundwater composition. In this study the results of some batch and leaching column tests, performed by means of Connelly iron (Environmental Technologies Inc., Canada) and different aqueous phases (distilled water and an artificial groundwater) are compared, to evaluate the influence of groundwater composition on the reactivity of the iron material for trichloroethylene (TCE) remediation. The degradation mechanisms of the pollutant are discussed. On the grounds of the gathered results the aqueous phase composition shows a strong influence on TCE degradation kinetics obtained by means of Connelly iron; in fact the presence of dissolved substances accelerates TCE degradation.
Determination of Aflatoxins in Peanuts, Maize Feed and Whole Milk by HPLC‐MS2 and MS3 Tandem Mass Spectrometry
Authors: Pazzi Marco , Medana Claudio , Brussino Mariacarla , Baiocchi Claudio
Published: October 2005

A method is presented for the detection of six toxins of fungal origin in various foods: peanuts, a sample of maize feed and whole milk. Extraction and HPLC‐APCI‐MS detection were discussed. The performances of MS/MS, MS3 and SRM detection modes were checked and best conditions of sensitivity were obtained in MS/MS mode.
Analysis of Voltammetric Data for the Evaluation of Seasonal Changes of the Ni, Cd, Pb and Cu Content in Atmospheric Particulate PM2.5
Authors: Giannetto Marco , Alfieri Enrica , Giugliano Michele , Lonati Giovanni , Mori Giovanni , Pizzol Massimo
Published: October 2005

In this paper, the preliminary results of a study on concentration of heavy metals in PM2.5 (atmospheric particles with aerodynamic diameter less than 2.5 μm) fractions of atmospheric particulate matter, sampled in Milan, are presented. This work aims to develop an electroanalytical method to analyse Pb, Cu, Cd and Ni in PM2.5 and to investigate seasonal and weekly trends in the amount of PM2.5 and its composition for considered metals. The samples have been selected within the seasons ranging from September 2002 to November 2003 so that they represent the possible seasonal changes; the samples within this period have been chosen in order to have data relevant to both working days and holidays. The determination of Cd, Pb and Cu has been carried out by Differential Pulse Anodic Stripping Voltammetry, whereas the concentration of Ni has been determined by Differential Pulse Adsorptive Cathodic Stripping Voltammetry. The concentrations of the metals in the sampled atmosphere and in the PM2.5 have been evaluated; through ANOVA possible seasonal or weekly variations in the above cited concentrations have been investigated.
Turner syndrome: Four challenges across the lifespan
Authors: Sutton Erica J. , McInerney‐Leo Aideen , Bondy Carolyn A. , Gollust Sarah E. , King Donnice , Biesecker Barbara
Published: October 2005

Turner syndrome (TS) is a sex chromosome condition that occurs in approximately 1/2,500 live female births. Despite the prevalence of this chromosomal condition, the challenges these women face throughout their lives are not fully understood. This qualitative research study aimed to characterize the subjective experiences of individuals with TS throughout their lifespan, to investigate their concerns and obstacles, and to offer insight into the strengths and weaknesses of health care delivery, as they perceived them. Ninety‐seven girls and women with TS and 21 parents consented to participate in this interview study. Interviews were semi‐structured and open‐ended in design. Questions sought to elicit responses relating to existing concerns associated with their condition and positive and negative health care experiences. Participants were divided into four age categories (childhood, adolescence, adulthood, and mature adulthood) to facilitate a comparative analysis across the age spectrum. Regardless of age, infertility was the most frequently cited concern followed closely by short stature. Sexual development and function and general health were also viewed as challenges by a number of participants in each age group. Although the relative weight of these four concerns tended to shift based upon the individual's age and life experiences, all four issues remained significant throughout the lifespan. Enhanced awareness of the evolving physical and psychological challenges faced by girls and women with TS may help health care providers (HCPs) improve the quality of life for these individuals. Published 2005 Wiley‐Liss, Inc.
Aberrant seizure‐induced neurogenesis in experimental temporal lobe epilepsy
Authors: Parent Jack M. , Elliott Robert C. , Pleasure Samuel J. , Barbaro Nicholas M. , Lowenstein Daniel H.
Published: October 2005

Neurogenesis in the hippocampal dentate gyrus persists throughout life and is increased by seizures. The dentate granule cell (DGC) layer is often abnormal in human and experimental temporal lobe epilepsy, with dispersion of the layer and the appearance of ectopic granule neurons in the hilus. We tested the hypothesis that these abnormalities result from aberrant DGC neurogenesis after seizure‐induced injury. Bromodeoxyuridine labeling, in situ hybridization, and immunohistochemistry were used to identify proliferating progenitors and mature DGCs in the adult rat pilocarpine temporal lobe epilepsy model. We also examined dentate gyri from epileptic human hippocampal surgical specimens. Prox‐1 immunohistochemistry and pulse‐chase bromodeoxyuridine labeling showed that progenitors migrate aberrantly to the hilus and molecular layer after prolonged seizures and differentiate into ectopic DGCs in rat. Neuroblast marker expression indicated the delayed appearance of chainlike progenitor cell formations extending into the hilus and molecular layer, suggesting that seizures alter migratory behavior of DGC precursors. Ectopic putative DGCs also were found in the hilus and molecular layer of epileptic human dentate gyrus. These findings indicate that seizure‐induced abnormalities of neuroblast migration lead to abnormal integration of newborn DGCs in the epileptic adult hippocampus, and implicate aberrant neurogenesis in the development or progression of recurrent seizures. Ann Neurol 2005
Design, Synthesis and Analysis of Inhibitors of Bacterial Aspartate Semialdehyde Dehydrogenase
Authors: Cox Russell J. , Gibson Jennifer S. , Hadfield Andrea T.
Published: October 2005

Unsaturated and fluorinated analogues of aspartyl‐β‐phosphate were synthesised as potential inhibitors of the bacterial enzyme aspartate semialdehyde dehydrogenase (ASA‐DH). Acetylenic and Z‐olefinic analogues showed competitive inhibition, but an E‐olefinic analogue was inactive. A monofluoromethylene phosphonate competed poorly, but showed time‐dependent inhibition of ASA‐DH in the absence of phosphate. Simulated docking procedures were used to rationalise the results. These studies showed that substrate and inhibitor binding are mediated by interaction with two active‐site arginine residues, and for likely covalent attachment to the active‐site thiol group, electrophilic carbon atoms should be located 4.5 Å, or less, from the thiol.
A Competitive Molecular Recognition Study: Syntheses and Analysis of Supramolecular Assemblies of 3,5‐Dihydroxybenzoic Acid and Its Bromo Derivative with Some N‐Donor Compounds
Authors: Varughese Sunil , Pedireddi Venkateswara Rao
Published: October 2005

A molecular recognition study of 3,5‐dihydroxybenzoic acid (1) and its bromo derivative 4‐bromo‐3,5‐dihydroxybenzoic acid (2) with the N‐donor compounds 1,2‐bis(4‐pyridyl)ethene (bpyee), 1,2‐bis(4‐pyridyl)ethane (bpyea), and 4,4′‐bipyridine (bpy) is reported. Thus, the syntheses and structural analysis of molecular adducts 1 a–1 c (1 with bpyee, bpyea, and bpy, respectively) and 2 a–2 c (2 with bpyee, bpyea, and bpy, respectively) are discussed. In all these adducts, recognition between the constituents is established through either OH⋅⋅⋅N and/or OH⋅⋅⋅N/CH⋅⋅⋅O pairwise hydrogen bonds. In all the adducts both OH and COOH functional groups available on 1 and 2 interact with the N‐donor compounds, except in 2 a, in which only COOH (COO−) is involved in the recognition process. The COOH moieties in 1 a, 1 b, and 2 b form only single OH⋅⋅⋅N hydrogen bonds, whereas in 1 c and 2 c, they form pairwise OH⋅⋅⋅N/CH⋅⋅⋅O hydrogen bonds. In addition, subtle differences in the recognition patterns resulted in the formation of cyclic networks of different dimensions. In fact, only 1 c forms a four‐molecule cyclic moiety, as was already documented in the literature for this kind of assemblies. All complexes have been characterized by single‐crystal X‐ray diffraction. The supramolecular architectures are quite elegant and simple, with stacking of sheets in all adducts, but a rather complex network with a threefold interpenetration pattern was found in 2 c.
Strahlungsinduzierte Reaktionen und Extraktion
Authors: Demel G. , Knauss R. , Rohde C. , Marr R. , Siebenhofer M.
Published: October 2005

Hybridprozesse gewinnen in der chemischen Synthese und Produkttrennung nicht zuletzt aus energetischen Überlegungen zunehmend an Bedeutung. Bekanntestes Beispiel für einen Hybridprozess ist die Reaktivrektifikation. Grundsätzlich ist die Kombination von chemischer Reaktion mit thermischem Trennverfahren auf alle thermischen Grundverfahren übertragbar. Weniger dokumentiert ist, welche Reaktionstypen für die Einbindung in einen Hybridprozess geeignet sind. Das gilt auch für photochemische Reaktionen. Um diese Kombination prüfen zu können, wurde experimentell die photoinduzierte Veresterung von Essigsäure mit Methanol mit überlagerter Flüssig/Flüssig‐Extraktion untersucht. Das Beispiel wurde als Modellreaktion gewählt, da diese Veresterungsreaktion selbst photochemisch nicht katalysiert werden kann. Erst die Wahl eines geeigneten Katalysators, der photochemisch aktivierbar ist, ermöglicht die Veresterung. Die Katalysatorwahl wurde auf marktübliche Photokatalysatoren, die durch Aktivierung Protonen bilden, eingeschränkt.
Zebrafish protocadherin 10 is involved in paraxial mesoderm development and somitogenesis
Authors: Murakami Tohru , Hijikata Takao , Matsukawa Miho , Ishikawa Harunori , Yorifuji Hiroshi
Published: October 2005

Here, we present the first report of the molecular cloning of zebrafish protocadherin 10 (Pcdh10, OL‐protocadherin) and describe its functional analyses in the development of segmental plate. Epitope‐tagged Pcdh10 expressed in embryos was localized on cell peripheries of adjacent cells. In situ hybridization showed that pcdh10 was expressed in the paraxial mesoderm (PAM) and developing somites, and in the pineal body, the diencephalon, and the vicinity of otocysts. Expression in PAM increased in the last few presumptive somites, reached the maximum level in the latest segmenting somites, and decreased thereafter during somite maturation. These expression patterns suggested that Pcdh10 is involved in development of PAM and somites. This was confirmed by morpholino knockdown and dominant‐negative inhibition of Pcdh10 in embryos, which disturbed movements of PAM cells and somite segmentation. Comparative studies showed that pcdh10 expression lasted up to approximately three times longer in maturing somites than that of paraxial protocadherin (pcdh8). They also indicated that the adaxial cells expressed pcdh8 but not pcdh10. We propose that Pcdh10 is involved in the morphogenic movements of PAM cells and somite segmentation and that differential adhesion of Pcdh8 and Pcdh10 plays a role in the morphogenic machinery of somites and adaxial cells. Developmental Dynamics 235:506–514, 2006. © 2005 Wiley‐Liss, Inc.
Help seeking and barriers to treatment in a community sample of Mexican American and European American women with eating disorders
Authors: Cachelin Fary M. , Striegel‐Moore Ruth H.
Published: October 2005

Objective

The study examined treatment seeking for eating disorders in Mexican American and European American women.

Method

One hundred forty‐five women with eating disorders (76 Mexican American, 69 European American) were diagnosed using the Structured Clinical Interview for DSM‐IV‐TR (SCID‐IV) and Eating Disorder Examination (EDE).

Results

Only 28% of the sample reported having sought treatment for their eating problems and only 17% had received treatment. Both groups were equally likely to believe they have significant eating problems and to want help. However, Mexican Americans were less likely to have sought treatment and, having sought help, were less likely to have been diagnosed or treated. European Americans were more likely to have utilized psychotherapists, psychiatrists, and psychotropic medications, whereas Mexican Americans largely had sought help from general practitioners for weight concern. The two groups endorsed similar barriers to treatment seeking.

Conclusion

Results support clinical impressions that eating disorders largely go undetected and untreated. Nonspecialists may be likely to fail to detect eating disorders. © 2005 by Wiley Periodicals, Inc.
Interaction of ICAM‐1 with β2‐integrin CD11c/CD18: Characterization of a peptide ligand that mimics a putative binding site on domain D4 of ICAM‐1
Authors: Frick Christoph , Odermatt Alex , Zen Ke , Mandell Kenneth J. , Edens Heather , Portmann Reto , Mazzucchelli Luca , Jaye David L. , Parkos Charles A.
Published: October 2005

The integrin CD11c/CD18 plays a role in leukocyte and cell matrix adhesion and is highly expressed in certain hematopoietic malignancies. To better characterize ligand binding properties, we panned random peptide phage‐display libraries over purified CD11c/CD18. We identified a phage expressing the circular peptide C‐GRWSGWPADL‐C. C‐GRWSGWPADL‐C phage bound specifically to CD11c/CD18 expressing monocytes but not CD11c/CD18 negative lymphocytes and showed 5 × 103‐fold higher binding to purified CD11c/CD18 than control phage, without binding to CD11b/CD18. Peptide sequence analysis revealed a similar sequence in domain D5 of ICAM‐1 and an alternative, phase‐shifted motif in domain D4. Surface plasmon resonance experiments demonstrated direct interaction of ICAM‐1 and CD11c/CD18. A soluble fusion protein containing the extracellular domain of ICAM‐1 abolished C‐GRWSGWPADL‐C phage binding to CD11c/CD18. Moreover, synthetic monomeric circular peptide C‐GRWSGWPADL‐C bound specifically to CD11c/CD18 and inhibited ICAM‐1 binding. Its rather low binding affinity and inability to displace pentavalent C‐GRWSGWPADL‐C phage from CD11c/CD18 suggests that a multimeric display of the selected peptide is essential for high affinity binding. Using ICAM‐1 deletion constructs, we showed that domain D4 is required for interaction with CD11c/CD18, suggesting that C‐GRWSGWPADL‐C phage binds specifically to CD11c/CD18 by structurally mimicking the interaction site on D4 of ICAM‐1.
Destructive potential of the aspartyl protease cathepsin D in MHC class II‐restricted antigen processing
Authors: Moss Catherine X. , Villadangos Jose A. , Watts Colin
Published: October 2005

Whether specific proteases influence MHC class II antigen presentation is still not clearly defined. Cathepsin D, one of the most abundant lysosomal proteases, is thought to be dispensable for MHC class II antigen presentation, yet in vitro digestions of antigen substrates with endosomes/lysosomes from antigen‐presenting cells sometimes reveal a dominant role for pepstatin‐sensitive aspartyl proteases of which cathepsin D is the major representative. We tested whether the aspartyl protease substrate myoglobin requires cathepsin D activity for presentation to T cells. Surprisingly, in dendritic cells (DC) lacking cathepsin D, presentation of two different myoglobin T cell epitopes was enhanced rather than hindered. This paradox is resolved by the finding that pepstatin‐sensitive myoglobin processing activity persists in lysosomes from cathepsin D‐null DC and that this reduced activity, most likely due to cathepsin E, is closer to the optimum level required for myoglobin antigen presentation. Our results indicate redundancy among lysosomal aspartyl proteases and show that while processing activities can be productive for MHC class II T cell epitope generation at one level, they can become destructive above an optimal level.
A Synthetic Approach to Macrocyclic, Chiral Phosphane Derivatives with Crown‐Ether‐Like Structures
Authors: Theil Agnès , Hitce Julien , Retailleau Pascal , Marinetti Angela
Published: October 2005

(S,S)‐Bis(2‐hydroxypropyl)(phenyl)phosphane oxide has been prepared, either by ring‐opening of (S)‐propylene oxide with dilithio(phenyl)phosphane or by catalytic hydrogenation of bis(2‐oxopropyl)(phenyl)phosphane oxide, promoted by ruthenium/MeO‐BIPHEP. Catalytic hydrogenation also allowed the enantioselective synthesis of (R,R)‐bis(2‐phenyl‐2‐hydroxyethyl)(phenyl)phosphane oxide from the corresponding diketone. These bis(β‐hydroxyalkyl)phosphane derivatives are suitable chiral starting materials for the synthesis of 1‐phospha‐10‐aza‐18‐crown‐6 derivatives, the first examples of optically pure, crown‐ether‐like, phosphorus‐containing macrocycles. One of them has been characterised by X‐ray diffraction study. Complexation of Na+ by the crown ether moiety of the macrocyclic ring has been observed by 1H NMR analysis. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Effect of Gas Dilution on PEM Fuel Cell Performance and Impedance Response
Authors: Boillot M. , Bonnet C. , Jatroudakis N. , Carre P. , Didierjean S. , Lapicque F.
Published: October 2005

In this work, an experimental study of gas dilution on the performance of a polymer electrolyte membrane (PEM) fuel cell was carried out. Impedance spectra were analysed depending on the dilution of either hydrogen or oxygen by nitrogen. By comparison of the impedance spectra obtained, the three loops were attributed to hydrogen oxidation, oxygen reduction and a low frequency diffusion process. Hydrogen oxidation was shown to be more complicated when the anode side was fed by a simulated reforming gas than with the same dilution rate with nitrogen.
Hepatic Expression of ABC Transporters G5 and G8 Does Not Correlate With Biliary Cholesterol Secretion in Liver Transplant Patients *
Authors: Geuken Erwin , Visser Dorien S. , Leuvenink Henri G.D. , de Jong Koert P. , Peeters Paul M.J.G. , Slooff Maarten J.H. , Kuipers Folkert , Porte Robert J.
Published: October 2005

Abstract

The adenosine triphosphate (ATP)-binding cassette (ABC)-transporters ABCG5 and ABCG8 have been shown to mediate hepatic and intestinal excretion of cholesterol. In various (genetically modified) murine models, a strong relationship was found between hepatic expression of ABCG5/ABCG8 and biliary cholesterol content. Our study aimed to relate levels of hepatic expression of ABCG5 and ABCG8 to biliary excretion of cholesterol in man. From 24 patients who had received a liver transplant, bile samples were collected daily after transplantation over a 2-week period to determine biliary composition. Expression of ABCG5, ABCG8, MDR3, and BSEP was assessed by real-time polymerase chain reaction (PCR) in liver biopsy specimens collected before and after transplantation. Levels of hepatic ABCG5, ABCG8, and MDR3 messenger RNA (mRNA) were strongly correlated. After transplantation, the biliary secretion rate of cholesterol continuously increased, coinciding with gradual increases in bile salt and phospholipid secretion. In contrast, hepatic levels of ABCG5 and ABCG8 mRNA remained unchanged. Surprisingly, no correlation was found between the hepatic expression of ABCG5 and ABCG8 and rates of biliary cholesterol secretion, normalized for biliary phospholipid secretion. As expected, the concentration of biliary phospholipids correlated well with MDR3 expression.
In conclusion
, the strong relationship between ABCG5 and ABCG8 gene expression is consistent with the coordinate regulation of both genes, and in line with heterodimerization of both proteins into a functional transporter. Hepatic ABCG5/ABCG8 expression, at least during the early phase after transplantation, is not directly related to biliary cholesterol secretion in humans. This finding suggests the existence of alternative pathways for the hepatobiliary transport of cholesterol that are not controlled by ABCG5/ABCG8. (Hepatology 2005;42:1166–1174.)
Infection of Human Hepatocyte Chimeric Mouse With Genetically Engineered Hepatitis B Virus *
Authors: Tsuge Masataka , Hiraga Nobuhiko , Takaishi Hideki , Noguchi Chiemi , Oga Hiromi , Imamura Michio , Takahashi Shoichi , Iwao Eiji , Fujimoto Yoshifumi , Ochi Hidenori , Chayama Kazuaki , Tateno Chise , Yoshizato Katsutoshi
Published: October 2005

Abstract

Studies of hepatitis B virus (HBV) mutants have been hampered by the lack of a small animal model with long-term infection of cloned HBV. Using a mouse model in which liver cells were highly replaced with human hepatocytes that survived over a long time with mature human hepatocyte function, we performed transmission experiments of HBV. Human serum containing HBV and the virus produced in HepG2 cell lines that transiently or stably transfected with 1.4 genome length HBV DNA were inoculated. Genetically modified e-antigen–negative mutant strain also was produced and inoculated into the mouse model. A high-level (≈1010 copies/mL) viremia was observed in mice inoculated with HBV-positive human serum samples. The level of viremia tended to be high in mice with a continuously high human hepatocyte replacement index. High levels and long-lasting viremia also were observed in mice injected with the

in vitro

generated HBV. The viremia continued up to 22 weeks until death or killing. Passage experiments showed that the serum of these mice contained infectious HBV. Genetically engineered hepatitis B e antigen–negative mutant clone also was shown to be infectious. Lamivudine effectively reduced the level of viremia in these infected mice.
In conclusion
, this mouse model of HBV infection is a useful tool for the study of HBV virology and evaluation of anti-HBV drugs. Our results indicate that HBeAg is dispensable for active viral production and transmission. (Hepatology 2005;42:1046–1054.)
Transcriptional Profiling After Bile Duct Ligation Identifies PAI-1 as a Contributor to Cholestatic Injury in Mice *
Authors: Wang Hongtao , Vohra Bhupinder P.S. , Zhang Yan , Heuckeroth Robert O.
Published: October 2005

Abstract

Extrahepatic cholestasis leads to complex injury and repair processes that result in bile infarct formation, neutrophil infiltration, cholangiocyte and hepatocyte proliferation, extracellular matrix remodeling, and fibrosis. To identify early molecular mechanisms of injury and repair after bile duct obstruction, microarray analysis was performed on liver tissue 24 hours after bile duct ligation (BDL) or sham surgery. The most upregulated gene identified encodes plasminogen activator inhibitor 1 (PAI-1, Serpine 1), a protease inhibitor that blocks urokinase plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) activity. Because PAI-1, uPA, and tPA influence growth factor and cytokine processing as well as extracellular matrix remodeling, we evaluated the role of PAI-1 in cholestatic liver injury by comparing the injury and repair processes in wild-type (WT) and PAI-1–deficient (PAI-1−/−) mice after BDL. PAI-1−/− mice had fewer and smaller bile infarcts, less neutrophil infiltration, and higher levels of cholangiocyte and hepatocyte proliferation than WT animals after BDL. Furthermore, PAI-1−/− mice had higher levels of tPA activation and mature hepatocyte growth factor (HGF) after BDL than WT mice, suggesting that PAI-1 effects on HGF activation critically influence cholestatic liver injury. This was further supported by elevated levels of c-Met and Akt phosphorylation in PAI-1−/− mice after BDL.
In conclusion
, PAI-1 deficiency reduces liver injury after BDL in mice. These data suggest that inhibiting PAI-1 might attenuate liver injury in cholestatic liver diseases. (Hepatology 2005;42:1099–1108.)
High Prevalence of Spontaneous Portal-Systemic Shunts in Persistent Hepatic Encephalopathy: A Case-Control Study *
Authors: Riggio Oliviero , Efrati Cesare , Catalano Carlo , Pediconi Federica , Mecarelli Oriano , Accornero Neri , Nicolao Francesca , Angeloni Stefania , Masini Andrea , Ridola Lorenzo , Attili Adolfo F. , Merli Manuela
Published: October 2005

Abstract

Large spontaneous portal-systemic shunts have been occasionally described in patients with cirrhosis. This study was undertaken to assess the prevalence of portal-systemic shunts in patients with cirrhosis with recurrent or persistent hepatic encephalopathy (HE) as compared with patients with cirrhosis without HE. Fourteen patients with cirrhosis with recurrent or persistent HE (cases) and 14 patients with cirrhosis without previous or present signs of overt HE matching for age and degree of liver failure (controls) were studied. Each patient underwent neurological assessment and cerebral magnetic resonance (MR) imaging to exclude organic neurological pathological conditions. HE evaluation included psychometric performance (Trail-Making Test A), electroencephalogram (EEG), mental status examination and grading, arterial, venous, and partial pressure of ammonia determination. The presence of portal-systemic shunts was assessed by portal venous phase multidetector-row spiral computed tomography (CT). Large spontaneous portal-systemic shunts were detected in 10 patients with HE and in only 2 patients without HE (71% vs. 14%; chi square = 9.16;

df

= 1.0;

P

= .002). The patients with HE presented ascites (

P

= .002) and medium/large esophageal varices (

P

= .02) less frequently than the control group.
In conclusion
, our study suggests that large spontaneous shunts may often sustain the chronicity of HE; the presence of large shunts should be sought in patients with cirrhosis with recurrent or persistent HE. (Hepatology 2005;42:1158–1165.)
Human Monoclonal Antibodies That React With the E2 Glycoprotein of Hepatitis C Virus and Possess Neutralizing Activity *
Authors: Schofield Darren J. , Bartosch Birke , Shimizu Yohko K. , Allander Tobias , Alter Harvey J. , Emerson Suzanne U. , Cosset François-Loïc , Purcell Robert H.
Published: October 2005

Abstract

Active and/or passive immunoprophylaxis against hepatitis C virus (HCV) remain unachieved goals. Monoclonal antibodies might provide one approach to protection. We derived human monoclonal antibodies from the bone marrow of a patient with a well-controlled HCV infection of 22 years duration. Five distinct antibodies reactive with the E2 glycoprotein of the homologous 1a strain of HCV were recovered as antigen-binding fragments (FAbs). They demonstrated affinity constants as high as 2 nanomolar. “Neutralization of binding” titers paralleled the affinity constants. All five FAbs reacted with soluble E2 protein only in nonreducing gels, indicating that the relevant epitopes were conformational. The FAbs could be divided into two groups, based on competition analysis. Three of the FAbs neutralized the infectivity of pseudotyped virus particles (pp) bearing the envelope glycoproteins of the homologous HCV strain (genotype 1a). The three FAbs also neutralized genotype 1b pp and one also neutralized genotype 2a pp.
In conclusion
, one or more of these monoclonal antibodies may be useful in preventing infections by HCV belonging to genotype 1 or 2, the most medically important genotypes worldwide. (Hepatology 2005;42:1055–1062.)
Risk Factors and Comorbidities in Primary Biliary Cirrhosis: A Controlled Interview-Based Study of 1032 Patients *
Authors: Gershwin Eric M. , Selmi Carlo , Worman Howard J. , Gold Ellen B. , Watnik Mitchell , Utts Jessica , Lindor Keith D. , Kaplan Marshall M. , Vierling John M.
Published: October 2005

Abstract

Primary biliary cirrhosis (PBC) is an autoimmune disease of unknown etiology, often associated with other autoimmune conditions. Controlled studies have so far provided conflicting data on risk factors and comorbidity rates in PBC. We enrolled patients with PBC (n = 1032) from 23 tertiary referral centers for liver diseases in the United States and random-digit-dialed controls (n = 1041) matched for sex, age, race, and geographical location. Patients and controls were administered a modified version of the US National Health and Nutrition Examination Study (NHANES III) questionnaire by trained personnel to evaluate associations between PBC and social, demographic, personal and family medical histories, lifestyle, and reproductive factors and the rates of comorbidity in affected individuals. Data indicate that having a first-degree relative with PBC (adjusted odds ratio [AOR] 10.736; 95% confidence interval 4.227-27.268), history of urinary tract infections (AOR 1.511, 95% CI 1.192-1.915), past smoking (AOR 1.569, 95% CI 1.292-1.905), or use of hormone replacement therapies (AOR 1.548, 95% CI 1.273-1.882) were significantly associated with increased risk of PBC. The frequent use of nail polish slightly increased the risk of having PBC. Other autoimmune diseases were found in 32% of cases and 13% of controls (P<0.0001).
In conclusion
, environmental factors, possibly including infectious agents through urinary tract infections or chemicals contained in cigarette smoke, may induce PBC in genetically susceptible individuals. Exogenous estrogens may also contribute to explain the female predominance of the disease. (Hepatology 2005;42:1194–1202.)
Ethanol Metabolism Alters Interferon Gamma Signaling in Recombinant HepG2 Cells *
Authors: Osna Natalia A. , Clemens Dahn L. , Donohue Terrence M.
Published: October 2005

Abstract

We previously showed that IFNγ signal transduction was suppressed by ethanol in recombinant HepG2 cells (VL-17A cells), which express alcohol dehydrogenase (ADH) and CYP2E1. We examined the mechanisms by which STAT1 phosphorylation is blocked by ethanol treatment in VL-17A cells. Cells were exposed to 0 or 100 mmol/L ethanol for 72 hours. STAT1 phosphorylation was determined by Western blot after 1 hour IFNγ exposure. Reduction of STAT1 phosphorylation by ethanol was prevented in the presence of 4MP, DAS, or uric acid, indicating that the oxidative products from ethanol metabolism were partly responsible for suppression of STAT1 phosphorylation. Ethanol exposure decreased STAT1 tyrosine phosphorylation, whereas serine phosphorylation on the protein was unchanged. These effects of ethanol were mimicked by the peroxynitrite (PN) donor, SIN-1, which also blocked tyrosine, but not serine phosphorylation, on STAT1. When cells expressing either ADH (VA-13 cells) or CYP2E1 (E-47 cells) were exposed to ethanol, both ADH- and CYP2E1-generated products reduced STAT1 phosphorylation. In addition, SOCS1, a negative regulator of IFNγ signaling and which is degraded by the proteasome, was stabilized by ethanol treatment, presumably because of inhibited proteasome activity. Furthermore, SIN-1 treatment elevated SOCS1 levels in VL-17A cells, indicating that PN has a role in SOCS1 elevation.
In conclusion
, under conditions of ethanol-elicited oxidative stress, PN prevents STAT1 phosphorylation by stabilization of SOCS1, and possibly by nitration of tyrosine residues in STAT1 protein. (Hepatology 2005;42:1109–1117.)
δ13C tracing of dissolved inorganic carbon sources in Patagonian rivers (Argentina)
Authors: Brunet F. , Gaiero D. , Probst J. L. , Depetris P. J. , Gauthier Lafaye F. , Stille P.
Published: October 2005

The main Patagonian rivers (Colorado, Negro, Chubut, Deseado, Coyle, Chico, Santa Cruz and Gallegos) were sampled between September 1995 and November 1998 to determine their chemical and isotopic compositions, the origins of the suspended and dissolved river loads and their inputs to the South Atlantic Ocean. This paper focuses on the dissolved inorganic carbon (DIC) transport and its δ13C isotopic signature. The δ13CDIC values vary between −12·8 and −1·8‰ and allow one to distinguish two river groups: (i) the Colorado, Negro, Chubut and Santa Cruz, which display the highest values and the lowest seasonal variations; (ii) the Deseado, Coyle, Chico and Gallegos, which show the lowest values and the highest seasonal variations. For the first group, δ13CDIC is mainly controlled by important exchanges between the river waters and atmospheric CO2, due to the presence of lakes and dams. For the second group, δ13CDIC also appears to be controlled by the oxidation of organic carbon, showing a negative relationship between δ13CDIC and the dissolved organic carbon. These biogeochemical processes interfere with the contribution of carbonate and silicate weathering to the riverine DIC and do not allow use of δ13CDIC alone to distinguish these contributions.

The annual DIC flux exported by Patagonian Rivers to the South Atlantic Ocean averages 621 × 109 g. of C, i.e. a specific yield of 2·7 g m−2 year−1. The mean δ13CDIC can be estimated to − 4·9‰, which is high compared with other rivers of the world. Copyright © 2005 John Wiley & Sons, Ltd.
Isotope evolution and contribution to geochemical investigations in aquifer storage and recovery: a case study using reclaimed water at Bolivar, South Australia
Authors: Le Gal La Salle C. , Vanderzalm J. , Hutson J. , Dillon P. , Pavelic P. , Martin R.
Published: October 2005

Aquifer storage and recovery (ASR) is an important resource management tool whereby water from an available source is stored in a suitable aquifer for later use in periods of higher demand. Important issues in ASR include maintaining the injection rate and recovering water of suitable quality. Both of these depend on subsurface biogeochemical processes. This paper investigates the use of deuterium, 18O, 13C, 14C and 34S in understanding the reactions induced by reclaimed water injection in a carbonate aquifer at Bolivar, South Australia. Additionally, the injection scheme provides a natural laboratory to observe the process of carbon isotope exchange. The injectant deuterium (−6·4 ± 2·9‰ versus Vienna standard mean ocean water (V‐SMOW)) and 18O (−0·9 ± 0·5‰ V‐SMOW) signature is more enriched and variable than the native groundwater signature of −26 ± 1‰ and −4·4 ± 0·1‰ respectively. The variability of the injectant signature is maintained with injectant migration and is useful in constraining the portion of the injected end‐member reaching observation wells. Effluent treatment results in total dissolved inorganic carbon (TDIC) enriched in 13C (−3·3 ± 2·5‰ versus Pee Dee belemnite) and modern carbon (100 ± 7 per cent modern carbon (pmC)), which is distinct from the native groundwater comparatively depleted in 13C (−11 ± 1‰) and 14C (5·6 ± 2·1 pmC). The carbon isotopic signature in groundwater 4 m from the ASR well is dominated by the injectant signature modified by some organic matter oxidation and calcite dissolution. However, with further migration to the 50 m radius, both 13C and 14C signatures are dominated by isotopic exchange with the matrix surface (initially in equilibrium with the ambient groundwater) and little overall dissolution. During storage, biogeochemical processes, including sulphate reduction and methanogenesis, are dominant near the ASR well. These are indicated by a sulphate decline of up to 1·5 mmol l−1 with around 12‰ enrichment in the residual sulphate (versus Canyon Diablo troilite) and the addition of TDIC enriched in 13C, while maintaining a modern 14C activity. Copyright © 2005 John Wiley & Sons, Ltd.
Sulphur cycling in the drinking water catchment area of Torgau–Mockritz (Germany): insights from hydrochemical and stable isotope investigations
Authors: Knöller K. , Trettin R. , Strauch G.
Published: October 2005

The hydrochemical composition of groundwater and the isotopic composition of sulphur compounds in sediments (δ34S of sulphide, inorganic sulphate) and groundwater (δ34S, δ18O of dissolved sulphate) have been investigated to reveal the reasons for elevated concentrations of dissolved groundwater sulphate in the drinking water catchment area of Torgau–Mockritz (Germany).

The three most important anthropogenic sources of sulphate identified in this study are historic atmospheric sulphate deposition, predominantly of anthropogenic origin, inorganic fertilization, and dissolution of gypsum from waste dumps. Owing to their overlapping isotopic range, no clear differentiation between the individual anthropogenic sources is possible. Sulphate from the oxidation of sedimentary sulphides, however, was recognized by its negative sulphur isotope signature (δ34S < − 5‰).

The mobilization of sulphate from different soil sulphur species is closely connected with variable isotopic fractionations, resulting in a wide isotopic variation range for the sulphate entering the saturated zone. Generally, sulphur and oxygen isotope ratios of the dissolved groundwater sulphate range from −19 to +37‰ (Vienna Cañon Diablo troilite) and from −2 to +19‰ (Vienna standard mean ocean water), respectively. Sulphate from the majority of groundwater samples can be assigned to anthropogenic sources. Sulphate from sulphide oxidation is especially present in samples from the upper sampling level and the groundwater surface. Sulphate concentrations above 700 mg l−1 are mostly caused by the oxidation of sulphide. Sulphate that occurs in low and moderate concentrations dominantly originates from anthropogenic sources.

δ34S distribution patterns were used to locate the sources for the elevated sulphate concentrations in the raw water. It was shown that the sulphate is not mobilized in the immediate vicinity of the production wells. Rather, it originates in an area ∼1·5 km west of the intake. The main mobilization mechanism there is the oxidation of reduced sedimentary sulphur species.

Beyond its local significance, this study presents a general example how changes in the sulphur cycle indicate major, anthropogenically induced alterations of the hydrochemical situation in catchment areas. Copyright © 2005 John Wiley & Sons, Ltd.