bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulation and optimization of the continuous tower process for styrene polymerization
Authors: Bhat Shrikant A. , Sharma Rahul , Gupta Santosh K.
Published: August 2004

The continuous tower process, a popular industrial process for the manufacture of polystyrene, was simulated and optimized. A kinetic model for the thermal polymerization of styrene, which takes into account the Trommsdorff effect and the volume change accompanying the reaction, was developed. This was used to formulate model equations for the continuous flow stirred tank reactor (CSTR) and plug flow reactor (several sections) in the tower process. The model can predict monomer conversion, number‐ and weight‐average molecular weights, polydispersity index (PDI), and temperature at various locations in the unit, under specified operating conditions. Multiobjective optimization of this process was also carried out, for which an adaptation of a genetic algorithm (GA) was used. The two objectives were maximization of the final monomer conversion and minimization of the PDI of the product. The conversion in the CSTR was constrained to lie within a desired range, and polymer having a specified value of the number‐average molecular weight was to be produced. The optimal solution was a unique point (no Pareto sets were obtained). The optimal solutions indicated that the tower process is operated under near‐optimal conditions. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 775–788, 2004
Synthesis and characterization of novel polyesterimides
Authors: Shieh Jeng‐Yueh , Hsu Pei‐Hsuan , Wang Chun‐Shan
Published: August 2004

A series of soluble novel polyesterimides was synthesized from diamines [a mixture of 2,2‐bis(4‐(4‐aminophenoxy)phenyl)propane (BAPP) with amine‐terminated polysiloxane (ATPS) in various mole ratios] and the ester‐group‐containing dianhydrides. The ester group containing dianhydrides in turn was synthesized by the transesterification reaction of trimellitic anhydride (TMA) with diacetate ester of hydroquinone (HQ), 4,4′‐dihydrophenyl (BP), 1,6‐hexanediol, or ethylene glycol. The resulted polyesterimides were characterized by using Fourier‐transform infrared spectroscopy, inherent viscosity, solubility, differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The polyesterimides of BP and HQ had relatively high glass transition temperatures in the range of 214.7–227.2 and 195.7–210.5°C, respectively. The glass transitions decreased rather slowly with the increase in polysiloxane content. Thermal stability and the weight‐loss behavior of polyesterimides were studied by TGA. All polyesterimides of BP and HQ (BPI and HQI) showed no significant weight loss below 500°C in a N2 environment, and the decomposition temperatures (Td5%) of BPI and HQI were >520°C. Most polyesterimides were soluble in polar aprotic solvents and m‐cresol. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 730–738, 2004
Toward a basic framework for webometrics
Authors: Björneborn Lennart , Ingwersen Peter
Published: August 2004

In this article, we define webometrics within the framework of informetric studies and bibliometrics, as belonging to library and information science, and as associated with cybermetrics as a generic subfield. We develop a consistent and detailed link typology and terminology and make explicit the distinction among different Web node levels when using the proposed conceptual framework. As a consequence, we propose a novel diagram notation to fully appreciate and investigate link structures between Web nodes in webometric analyses. We warn against taking the analogy between citation analyses and link analyses too far.
Formally citing the Web
Authors: Wouters Paul , Vries Repke de
Published: August 2004

How do authors refer to Web‐based information sources in their formal scientific publications? It is not yet well known how scientists and scholars actually include new types of information sources, available through the new media, in their published work. This article reports on a comparative study of the lists of references in 38 scientific journals in five different scientific and social scientific fields. The fields are sociology, library and information science, biochemistry and biotechnology, neuroscience, and the mathematics of computing. As is well known, references, citations, and hyperlinks play different roles in academic publishing and communication. Our study focuses on hyperlinks as attributes of references in formal scholarly publications. The study developed and applied a method to analyze the differential roles of publishing media in the analysis of scientific and scholarly literature references. The present secondary databases that include reference and citation data (the Web of Science) cannot be used for this type of research. By the automated processing and analysis of the full text of scientific and scholarly articles, we were able to extract the references and hyperlinks contained in these references in relation to other features of the scientific and scholarly literature. Our findings show that hyperlinking references are indeed, as expected, abundantly present in the formal literature. They also tend to cite more recent literature than the average reference. The large majority of the references are to Web instances of traditional scientific journals. Other types of Web‐based information sources are less well represented in the lists of references, except in the case of pure e‐journals. We conclude that this can be explained by taking the role of the publisher into account. Indeed, it seems that the shift from print‐based to electronic publishing has created new roles for the publisher. By shaping the way scientific references are hyperlinking to other information sources, the publisher may have a large impact on the availability of scientific and scholarly information.
Transposition of the cocitation method with a view to classifying Web pages
Authors: Prime‐Claverie Camille , Beigbeder Michael , Lafouge Thierry
Published: August 2004

The Web is a huge source of information, and one of the main problems facing users is finding documents which correspond to their requirements. Apart from the problem of thematic relevance, the documents retrieved by search engines do not always meet the users' expectations. The document may be too general, or conversely too specialized, or of a different type from what the user is looking for, and so forth. We think that adding metadata to pages can considerably improve the process of searching for information on the Web. This article presents a possible typology for Web sites and pages, as well as a method for propagating metadata values, based on the study of the Web graph and more specifically the method of cocitation in this graph.
Understanding the Nature of the Molecular Mechanisms Associated with the Competitive Lewis Acid Catalyzed [4+2] and [4+3] Cycloadditions between Arylidenoxazolone Systems and Cyclopentadiene: A DFT Analysis
Authors: Arnó Manuel , Picher M. Teresa , Domingo Luis R. , Andrés Juan
Published: August 2004

The molecular mechanisms of the reactions between aryliden‐5(4H)‐oxazolone 1, and cyclopentadiene (Cp), in presence of Lewis acid (LA) catalyst to obtain the corresponding [4+2] and [4+3] cycloadducts are examined through density functional theory (DFT) calculations at the B3LYP/6‐31G* level. The activation effect of LA catalyst can be reached by two ways, that is, interaction of LA either with carbonyl or carboxyl oxygen atoms of 1 to render [4+2] or [4+3] cycloadducts. The endo and exo [4+2] cycloadducts are formed through a highly asynchronous concerted mechanism associated to a Michael‐type addition of Cp to the β‐conjugated position of α,β‐unsaturated carbonyl framework of 1. Coordination of LA catalyst to the carboxyl oxygen yields a highly functionalized compound, 3, through a domino reaction. For this process, the first reaction is a stepwise [4+3] cycloaddition which is initiated by a Friedel–Crafts‐type addition of the electrophilically activated carbonyl group of 1 to Cp and subsequent cyclization of the corresponding zwitterionic intermediate to yield the corresponding [4+3] cycloadduct. The next rearrangement is the nucleophilic trapping of this cycloadduct by a second molecule of Cp to yield the final adduct 3. A new reaction pathway for the [4+3] cycloadditions emerges from the present study.
Highly Effective Sulfated Zirconia Nanocatalysts Grown out of Colloidal Silica at High Temperature
Authors: Zhu Guangshan , Wang Ce , Zhang Yahong , Guo Na , Zhao Yiyang , Wang Runwei , Qiu Shilun , Wei Yen , Baughman Ray H.
Published: August 2004

A large surface‐to‐volume ratio is a prerequisite for highly effective catalysts. Making catalysts in the form of nanoparticles provides a good way to achieve the aim. However, agglomeration of nanoparticles during the preparation and utilization of nanocatalysts remains a formidable problem. Here, we present a novel approach in which nano units of catalysts are formed in the matrix of a colloidal carrier, with assistance of a cross‐linking agent, and then grow out of the carrier upon calcination at high temperature. This ensures that the catalysts not only do not agglomerate, but also have a low cost and high catalytic efficiency due to the large surface‐to‐volume ratio and the absence of carbon deposition. The technique is demonstrated by the successful preparation of a binary nanocatalyst that consists of a silica nanoparticle core and a sulfated zirconia (SZ) nanocrystal shell (JML‐1). The synthesis was achieved by converting sulfated zirconia (SZ) and silica solutions into a composite gel by means of sol–gel processing in the presence of triethoxysilane as the cross‐linking agent, followed by heating at 50 °C and calcining at 550 °C. Relative to other catalysts, such as pure SZ, non‐nanodispersed SZ over silica (SZ/SiO2), and zeolites Y, Beta, and ZSM‐5, JML‐1 exhibits superior catalytic activity in many reactions. For example, the activity of JML‐1 in the production of gasoline by alkylation of 1‐butene with isobutene remained at 95 % or higher after 20 h of reaction and was over 90 % after being regenerated five times. In sharp contrast, SZ and SZ/SiO2 give a high activity only for 2 h and the initial activity of zeolites Beta and ZSM‐5 are about 88 and 60 %, respectively. These findings demonstrate that non‐agglomerated nanoparticles anchored onto a carrier surface can be prepared and the technique provides a versatile route to new highly effective nanocatalyst systems.
Immunophenotypic and molecular features, clinical outcomes, treatments, and prognostic factors associated with subcutaneous panniculitis‐like T‐cell lymphoma
Authors: Go Ronald S. , Wester Susan M.
Published: August 2004

BACKGROUND

Subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL) is an uncommon type of skin lymphoma. The natural history, optimal treatment strategy, and prognostic factors associated with this malignancy are not well defined.

METHODS

The authors performed a systematic analysis of all patients with SPTCL reported on in the English‐language medical literature, with emphasis on specific clinical features, experiences involving the use of radiotherapy and systemic agents, and prognostic factors predictive of treatment response and clinical outcome.

RESULTS

One hundred fifty‐six patients with SPTCL were identified in the literature. Hemophagocytic syndrome (HPS) was a presenting feature in 37% of patients, and > 90% of patients required treatment at diagnosis. Prednisone was used frequently as initial therapy in patients who had less aggressive disease at presentation; however, durable complete remissions (CR) were infrequent. Anthracycline‐based chemotherapy regimens were the most commonly used and most effective systemic treatment options, producing long‐term CR in ∼30% of patients. Among patients who received high‐dose chemotherapy and stem cell transplantation (HDT‐SCT) for refractory or recurrent disease, 92% achieved CR, with a median response duration of ≥ 14 months. The presence of HPS at diagnosis and expression of the γ/δ T‐cell receptor (TCR) by tumor cells were associated with poor survival, whereas age was not. After a median follow‐up of 24 months, 48% of patients died of disease. The median survival duration was 27 months.

CONCLUSIONS

SPTCL has an aggressive natural history. Nonetheless, a subgroup of patients with SPTCL can have long‐term disease remission following anthracycline‐based initial therapy or subsequent HDT‐SCT. HPS and the TCR phenotype may be useful prognostic markers for patients with this malignancy. Cancer 2004. © 2004 American Cancer Society.
Value of routine follow‐up for patients cured of laryngeal carcinoma
Authors: Ritoe Savitri C. , Krabbe Paul F. M. , Kaanders Johannes H. A. M. , van den Hoogen Frank J. A. , Verbeek André L. M. , Marres Henri A. M.
Published: August 2004

BACKGROUND

Routine follow‐up offered to patients with laryngeal carcinoma in The Netherlands consisted of 22 routine visits over a time period of 10 years after treatment. The primary aims of the follow‐up were to detect cancer recurrence in asymptomatic patients and to achieve better survival outcome by reducing cancer‐specific mortality rates.

METHODS

A longitudinal cohort study was performed to evaluate the effect of this follow‐up schedule. Between January 1990 and January 1995, the authors studied all patients with primary laryngeal squamous cell carcinoma who were treated with intention to cure. For patients who developed cancer recurrence, all routine and extra visits were documented. Reported symptoms and physical evidence of tumor were mapped.

RESULTS

The patients complied with the follow‐up protocol closely. In only 2% of all routine visits an asymptomatic cancer recurrence was found. There was no difference in survival and tumor mortality rates for patients with and without symptoms, despite the difference in whether the therapy applied had the intention to cure. It seemed that patients who developed tumor recurrence after therapy for laryngeal carcinoma received no benefit from screening for cancer recurrence detection. The lack of benefit for cancer detection screening among asymptomatic patients might be explained by unfavorable tumor biology parameters.

CONCLUSIONS

The routine follow‐up program after treatment for laryngeal carcinoma did not lead to survival benefit for asymptomatic patients with tumor recurrence. Cancer 2004. © 2004 American Cancer Society.
Non‐Haloaluminate Room‐Temperature Ionic Liquids in Electrochemistry—A Review
Authors: Buzzeo Marisa C. , Evans Russell G. , Compton Richard G.
Published: August 2004

Some twenty‐five years after they first came to prominence as alternative electrochemical solvents, room temperature ionic liquids (RTILs) are currently being employed across an increasingly wide range of chemical fields. This review examines the current state of ionic liquid‐based electrochemistry, with particular focus on the work of the last decade. Being composed entirely of ions and possessing wide electrochemical windows (often in excess of 5 volts), it is not difficult to see why these compounds are seen by electrochemists as attractive potential solvents. Accordingly, an examination of the pertinent properties of ionic liquids is presented, followed by an assessment of their application to date across the various electrochemical disciplines, concluding with an outlook viewing current problems and directions.
Identification of Biotic and Abiotic Particles by Using a Combination of Optical Tweezers and In Situ Raman Spectroscopy
Authors: Geßner R. , Winter C. , Rösch P. , Schmitt M. , Petry R. , Kiefer W. , Lankers M. , Popp J.
Published: August 2004

A highly versatile setup, which introduces an optical gradient trap into a Raman spectrometer, is presented. The particular configuration, which consists of two lasers, makes trapping independent from the Raman excitation laser and allows a separate adjustment of the trapping and excitation wavelengths. Thus, the excitation wavelength can be chosen according to the needs of the application. We describe the successful application of an optical gradient trap on transparent as well as on reflective, metal‐coated microparticles. Raman spectra were recorded from optically trapped polystyrene beads and from single biological cells (e.g., erythrocytes, yeast cells). Also, metal‐coated microparticles were trapped and used as surface enhanced Raman spectroscopy (SERS) substrates for tests on yeast cells. Furthermore, the optical gradient trap was combined with a SERS fiber probe. Raman spectra were recorded from trapped red blood cells using the SERS fiber probe for excitation.
A Novel Fluorophore with Dual Fluorescence: Local Excited State and Photoinduced Electron‐Transfer‐Promoted Charge‐Transfer State
Authors: Thiagarajan Viruthachalam , Selvaraju Chellappan , Malar E. J. Padma , Ramamurthy Perumal
Published: August 2004

Absorption and emission spectra of 9‐N,N‐dimethylaniline decahydroacridinedione (DMAADD) have been studied in different solvents. The fluorescence spectra of DMAADD are found to exhibit dual emission in aprotic solvents and single emission in protic solvents. The effect of solvent polarity and viscosity on the absorption and emission spectra has also been studied. The fluorescence excitation spectra of DMAADD monitored at both the emission bands are different. The presence of two different conformation of the same molecule in the ground state has lead to two close lying excited states, local excited (LE) and charge transfer (CT), and thereby results in the dual fluorescence of the dye. A CT state involving the N,N‐dimethylaniline group and the decahydroacridinedione chromophore as donor and acceptor, respectively, has been identified as the source of the long wavelength anomalous fluorescence. The experimental studies were supported by ab initio time dependent‐density functional theory (TD‐DFT) calculations performed at the B3LYP/6–31G* level. The molecule possesses photoinduced electron transfer (PET) quenching in the LE state, which is confirmed by the fluorescence lifetime and fluorescent intensity enhancement in the presence of transition metal ions.
Biomolecule‐Functionalized Carbon Nanotubes: Applications in Nanobioelectronics
Authors: Katz Eugenii , Willner Itamar
Published: August 2004

Carbon nanotubes (CNTs) revealing metallic or semiconductive properties depending on the folding modes of the nanotube walls represent a novel class of nanowires. Different methods to separate semiconductive CNTs from conductive CNTs have been developed, and synthetic strategies to chemically modify the side walls or tube ends by molecular or biomolecular components have been reported. Tailoring hybrid systems consisting of CNTs and biomolecules (proteins and DNA) has rapidly expanded and attracted substantial research effort. The integration of biomaterials with CNTs enables the use of the hybrid systems as active field‐effect transistors or biosensor devices (enzyme electrodes, immunosensors, or DNA sensors). Also, the integration of CNTs with biomolecules has allowed the generation of complex nanostructures and nanocircuitry of controlled properties and functions. The rapid progress in this interdisciplinary field of CNT‐based nanobioelectronics and nanobiotechnology is reviewed by summarizing the present scientific accomplishments, and addressing the future goals and perspectives of the area.
Identification of recessive maternal‐effect mutations in the zebrafish using a gynogenesis‐based method
Authors: Pelegri Francisco , Dekens Marcus P.S. , Schulte‐Merker Stefan , Maischein Hans‐Martin , Weiler Catrin , Nüsslein‐Volhard Christiane
Published: August 2004

In animal species, early developmental processes are driven by maternally derived factors. Here, we describe a forward genetics approach to identify recessive mutations in genes encoding such maternal factors in the zebrafish. We used a gynogenesis‐based approach to identify 14 recessive maternal‐effect mutations. Homozygosity for these mutations in adult females leads to the inviability of their offspring. Confocal microscopy of embryos labeled with a DNA dye and a membrane marker allowed us to further analyze mutant embryos for defects in nuclear and cellular divisions. The mutations result in a range of defects in early developmental processes, including egg activation, early nuclear events, mitosis, cytokinesis, axial patterning, and gastrulation. Our effort constitutes a systematic attempt to identify maternal‐effect genes in a vertebrate species. The sample of mutations that we have identified reflects the diversity of maternally driven functions in early development and underscores the importance of maternal factors in this process. Developmental Dynamics 231:324–335, 2004. © 2004 Wiley‐Liss, Inc.
Human in vivo‐activated CD45R0+ CD4+ T cells are susceptible to spontaneous apoptosis that can be inhibited by the chemokine CXCL12 and IL‐2, ‐6, ‐7, and ‐15
Authors: Pajusto Mervi , Ihalainen Niina , Pelkonen Jukka , Tarkkanen Jussi , Mattila Petri S.
Published: August 2004

The number of T cells that have undergone proliferation after antigen stimulation in vivo must be controlled to prevent excessive accumulation of T cells, autoimmunity, and T cell neoplasia. We describe here that primary human adenotonsillar memory phenotype CD45R0+ CD4+ T cells, but not adenotonsillar naive‐phenotype CD45RA+ CD4+ T cells, or peripheral blood naive or memory CD4+ T cells, express high levels of activation‐associated antigens CD38, CD69, CD71, and HLA‐DR. These in vivo‐activated CD45R0+ CD4+ T cells were susceptible to spontaneous and rapid apoptosis in vitro. Apoptosis could not be inhibited by the disruption of Fas‐Fas ligand engagement or by the pan‐caspase inhibitor ZVAD. Cross‐linking of the T cell antigen receptor did not rescue cells from apoptosis. Apoptosis could be partially inhibited by the chemokine CXCL12/SDF‐1, by IL‐6, and by the IL‐2 receptor common γ chain‐signaling cytokines IL‐2, ‐7, and ‐15. Inhibitors of phosphatidylinositol 3‐kinase accelerated apoptosis. We conclude that after in vivo activation of CD45R0+ CD4+ T cells, the cells experience a period of intrinsically elevated sensitivity to apoptosis and that multiple external signals control their survival.
Comparative analysis of NK cell subset distribution in normal and lymphoproliferative disease of granular lymphocyte conditions
Authors: Pascal Véronique , Schleinitz Nicolas , Brunet Corinne , Ravet Sophie , Bonnet Elodie , Lafarge Xavier , Touinssi Mhammed , Reviron Denis , Viallard Jean Francois , Moreau Jean Francois , Déchanet‐Merville Julie , Blanco Patrick , Harlé Jean Robert , Sampol José , Vivier Eric , Dignat‐George Françoise , Paul Pascale
Published: August 2004

We have characterized the heterogeneity of human blood NK cell subsets defined by expression of KIR, lectin like receptors and NK cell differentiation markers within a cohort of 51 healthy Caucasian individuals. High inter‐individual variability in cell surface expression of most NK cell markers is observed. Range values defining NK cell subsets in healthy donors were further used as references to characterize 14 patients with NK‐type lymphoproliferative disease of granular lymphocytes (NK‐LDGL). Alterations of the KIR repertoire were noted in all NK‐LDGL patients. NK cell expansions were classified as oligoclonal KIR+ or as non‐detectable KIR (ndKIR) using anti‐KIR2DL1/2DS1, anti‐KIR2DL2/2DL3/2DS2, anti‐KIR3DL1 and anti‐KIR2DS4 monoclonal antibodies. A major reduction in the size of the CD56bright NK cell subset was a constant feature of NK‐LDGL. Altered distribution of CD94+, CD161+, and CD162R+ NK cell subsets was also observed in NK‐LDGL patients. Considering the potential role of NK cells in eliminating tumors or virus‐infected cells, the reference values defined in this study should be valuable to characterize both quantitative and qualitative alterations of the NK cell repertoire in pathological conditions and to monitor NK cell reconstitution following hematopoietic transplantation.
Early cytoskeletal rearrangement during dendritic cell maturation enhances synapse formation and Ca2+ signaling in CD8+ T cells
Authors: Averbeck Marco , Braun Thorsten , Pfeifer Gunther , Sleeman Jonathan , Dudda Jan , Martin Stefan F. , Kremer Bernhard , Aktories Klaus , Simon Jan C. , Termeer Christian
Published: August 2004

The interplay between dendritic cells (DC) and T cells is a dynamic process critically depending on DC maturation. Ca2+ influx is one of the initial events occurring during DC/T cell contacts. To determine how DC maturation influences DC/T cell contacts, time‐lapse video microscopy was established using TCR‐transgenic CD8+ T cells from P14 mice. DC maturation shifted DC/T cell contacts from short‐lived interactions with transient Ca2+ influx in T cells to long‐lasting interactions and sustained Ca2+ influx of 30 min and more. Follow‐up of DC/T cell interactions after 2 h using confocal microscopy revealed that long‐lasting Ca2+ responses in T cells were preferentially associated with the formation of an immunological synapse involving CD54 and H2‐Kb at the DC/T cell interface. Such synapse formation preceded MHC or B7 up‐regulation, since DC developed into potent Ca2+ stimulators 7 h after initiation of maturation. Instead, the enhanced capacity of 7 h‐matured DC to induce sustained Ca2+ responses in CD8+ T cells is critically dependent on the polarization and rearrangement of the cytoskeleton, as shown by Clostridium difficile toxin B inhibitor experiments. These data indicate that already very early after receiving a maturation stimulus, DC display enhanced cytoskeletal activity resulting in the rapid formation of immunological synapses and effective CD8+ T cell stimulation.
A role for lymphotoxin in the acquisition of Ly49 receptors during NK cell development
Authors: Lian Rebecca H. , Chin Robert K. , Nemeth Hajnalka E. , Libby Shon L. , Fu Yang‐Xin , Kumar Vinay
Published: August 2004

NK cells lyse tumor, virus‐infected and allogeneic cells through a recognition system involving inhibitory and activating receptors, among which are the Ly49 molecules that recognize MHC class I proteins. To date, little is known about the regulation of Ly49 expression during NK cell development. In this study we report that the acquisition of Ly49 receptors by NK cells is significantly reduced in lymphotoxin (LT) α‐deficient mice, whereas it is increased in LTα transgenic mice. Treating normal mice with LTβR‐Ig fusion protein reduced Ly49 expression, indicating that regulation of Ly49 receptor expression occurs through the engagement of membrane LT to LTβR, and not soluble LT to TNFR. In addition, when LTα–/– mice were treated exogenously with recombinant IL‐15, NK cell numbers as well as Ly49 acquisition were restored to wild‐type levels. Finally, using real‐time PCR analyses of bone marrow cells obtained from LT‐deficient or transgenic mice, we show a direct correlation between LTβR activation and increased IL‐15 transcription. These data suggest that LTβR‐mediated signals regulate Ly49 expression at least in part through the activation of IL‐15.
Long‐run forecasting in multicointegrated systems
Authors: Siliverstovs Boriss , Engsted Tom , Haldrup Niels
Published: August 2004

We extend the analysis of Christoffersen and Diebold (1998) on long‐run forecasting in cointegrated systems to multicointegrated systems. For the forecast evaluation we consider several loss functions, each of which has a particular interpretation in the context of stock‐flow models where multicointegration typically occurs. A loss function based on a standard mean square forecast error (MSFE) criterion focuses on the forecast errors of the flow variables alone. Likewise, a loss function based on the triangular representation of cointegrated systems (suggested by Christoffersen and Diebold) considers forecast errors associated with changes in both stock (modelled through the cointegrating restrictions) and flow variables. We suggest a new loss function based on the triangular representation of multicointegrated systems which further penalizes deviations from the long‐run relationship between the levels of stock and flow variables as well as changes in the flow variables. Among other things, we show that if one is concerned with all possible long‐run relations between stock and flow variables, this new loss function entails high and increasing forecasting gains compared to both the standard MSFE criterion and Christoffersen and Diebold's criterion. This paper demonstrates the importance of carefully selecting loss functions in forecast evaluation of models involving stock and flow variables. Copyright © 2004 John Wiley & Sons, Ltd.
Delayed degradation of parental macronuclear DNA in programmed nuclear death of Paramecium caudatum
Authors: Kimura Naomi , Mikami Kazuyuki , Endoh Hiroshi
Published: August 2004

In the ciliated protozoan Paramecium caudatum, a parental macronucleus that is fragmented into some 40–50 pieces during conjugation does not degenerate immediately, but persists until the eighth cell cycle after conjugation. Here we demonstrate that the initiation of the parental macronuclear degeneration occurs at about the fifth cell cycle. The size of parental macronuclear fragments continued to increase between the first and fourth cell cycle, but gradually decreased thereafter. By contrast, a new macronucleus grew and reached a maximum size by the fourth cell cycle, suggesting that the new macronucleus matured by that stage. Southern blot analysis revealed that parental macronuclear DNA was degraded at about the fifth cell cycle. The degradation was supported by acridine orange staining, indicating degeneration of the macronuclear fragments. Prior to the degradation, the fragments once attached to the new macronucleus were subsequently liberated from it. These observations lead us to conclude that once a new macronucleus has been fully formed by the fourth cell cycle, the parental macronuclear fragments are destined to degenerate, probably through direction by new macronucleus. Considering the long persistence of the parental macronucleus during the early cell cycles after conjugation, the macronuclear fragments might function in the maturation of the imperfect new macronucleus. Two possible functions, a gene dosage compensation and adjustment of ploidy level, are discussed. genesis 40:15–21, 2004. © 2004 Wiley‐Liss, Inc.
The implications of linking questions within the SG and TTO methods
Authors: Spencer Anne
Published: August 2004

We consider the impact of introducing intermediate stages, chained together, into the standard gamble (SG) and time trade‐off (TTO) methods. Less is known about the impact of intermediate stages, chained together, in the TTO method. We broadly replicate the patterns of responses observed in other SG studies which have been accounted for by loss aversion. We find that the TTO responses do not replicate the patterns found in the SG responses. The results support the notion that additional issues arise in the TTO method that counteract loss aversion. Copyright © 2004 John Wiley & Sons, Ltd.
Kupffer cell-derived interleukin 10 is responsible for impaired bacterial clearance in bile duct-ligated mice
Authors: Abe Tetsuya , Arai Toshiyuki , Ogawa Atsushi , Hiromatsu Takashi , Masuda Akio , Matsuguchi Tetsuya , Nimura Yuji , Yoshikai Yasunobu
Published: August 2004

Extrahepatic cholestasis often evokes liver injury with hepatocyte apoptosis, aberrant cytokine production, and—most importantly—postoperative septic complications. To clarify the involvement of aberrant cytokine production and hepatocyte apoptosis in impaired resistance to bacterial infection in obstructive cholestasis, C57BL/6 mice or Fas-mutated lpr mice were inoculated intraperitoneally with 107 colony-forming units of Escherichia coli 5 days after bile duct ligation (BDL) or sham celiotomy. Cytokine levels in sera, liver, and immune cells were assessed via enzyme-linked immunosorbent assay or real-time reverse-transcriptase polymerase chain reaction. BDL mice showed delayed clearance of E. coli in peritoneal cavity, liver, and spleen. Significantly higher levels of serum interleukin (IL) 10 with lower levels of IL-12p40 were observed in BDL mice following E. coli infection. Interferon γ production from liver lymphocytes in BDL mice was not increased after E. coli infection either at the transcriptional or protein level. Kupffer cells from BDL mice produced low levels of IL-12p40 and high levels of IL-10 in vitro in response to lipopolysaccharide derived from E. coli. In vivo administration of anti-IL-10 monoclonal antibody ameliorated the course of E. coli infection in BDL mice. Furthermore, BDL-lpr mice did not exhibit impairment in E. coli killing in association with little hepatic injury and a small amount of IL-10 production. In conclusion, increased IL-10 and reciprocally suppressed IL-12 production by Kupffer cells are responsible for deteriorated resistance to bacterial infection in BDL mice. Fas-mediated hepatocyte apoptosis in cholestasis may be involved in the predominant IL-10 production by Kupffer cells. (Hepatology 2004;40:414-423.)
Diverse regulation of NF-κB and peroxisome proliferator-activated receptors in murine nonalcoholic fatty liver
Authors: Romics Laszlo , Kodys Karen , Dolganiuc Angela , Graham Lucia , Velayudham Arumugam , Mandrekar Pranoti , Szabo Gyongyi
Published: August 2004

Fatty liver is highly sensitive to inflammatory activation. Peroxisome proliferator-activated receptors (PPAR) have anti-inflammatory effects and regulate lipid metabolism in the fatty liver. We hypothesized that fatty liver leads to endotoxin sensitivity through an imbalance between pro- and anti-inflammatory signals. Leptin-deficient, ob/ob mice and their lean littermates were challenged with single or double insults and pro- and anti-inflammatory pathways were tested on cytokine production and activation of nuclear regulatory factors NF-κB and peroxisome proliferator receptor element (PPRE). Ob/ob mice produced significantly higher serum tumor necrosis factor α (TNF-α) and interleukin (IL) 6 and showed increased hepatic NF-κB activation compared to lean littermates after stimulation with a single dose of lipopolysaccharide (LPS) or alcohol. In ob/ob mice, double insults with alcohol and LPS augmented proinflammatory responses mediated by increased degradation of inhibitory κB (IκB)-α and IκB-β and preferential induction of the p65/p50 NF-κB heterodimer. In lean mice, in contrast, acute alcohol attenuated LPS-induced TNF-α, IL-6 production, and NF-κB activation through reduced IκB-α degradation and induction of p50/p50 homodimers. PPRE binding was increased in fatty but not in lean livers after alcohol or LPS stimulation. However, cotreatment with alcohol and LPS reduced both PPRE binding and nuclear levels of PPAR-α in fatty livers but increased those in lean livers. In conclusion, our results show opposite PPRE and NF-κB activation in fatty and lean livers. PPAR activation may represent an anti-inflammatory mechanism that fails in the fatty liver on increased proinflammatory pressure. Thus, an imbalance between PPAR-mediated anti-inflammatory and NF-κB-mediated proinflammatory signals may contribute to increased inflammation in the fatty liver. (Hepatology 2004;40:376-385.)
Performance standards for therapeutic abdominal paracentesis
Authors: Grabau Catherine M. , Crago Sharon F. , Hoff Linda K. , Simon Julie A. , Melton Cheryl A. , Ott Beverly J. , Kamath Patrick S.
Published: August 2004

Large-volume paracentesis, the preferred treatment for patients with symptomatic tense ascites due to cirrhosis, has traditionally been performed by physicians as an inpatient procedure. Our objectives were to determine (1) whether large-volume paracentesis could be performed safely and effectively by gastrointestinal endoscopy assistants and as an outpatient procedure, (2) whether the risk of bleeding was associated with either thrombocytopenia or prolongation of the prothrombin time, and (3) the resources used for large-volume paracentesis. Gastrointestinal endoscopy assistants performed 1,100 large-volume paracenteses in 628 patients, 513 of whom had cirrhosis of the liver. The preprocedure mean international normalized ratio for prothrombin time was 1.7 ± 0.46 (range, 0.9-8.7; interquartile range, 1.4-2.2), and the mean platelet count was 50.4 × 103/μL, (range, 19 × 103/μL − 341 × 103/μL; interquartile range, 42-56 × 103/μL). Performance of 3 to 7 supervised paracenteses was required before competence was achieved. There were no significant procedure-related complications, even in patients with marked thrombocytopenia or prolongation in the prothrombin time. The mean duration of large-volume paracentesis was 97 ± 24 minutes, and the mean volume of ascitic fluid removed was 8.7 ± 2.8 L. In conclusion, large-volume paracentesis can be performed safely as an outpatient procedure by trained gastrointestinal endoscopy assistants. Ten supervised paracenteses would be optimal for training the operators carrying out the procedure. The practice guideline of the American Association for the Study of Liver Diseases which states that routine correction of prolonged prothrombin time or thrombocytopenia is not required is appropriate when experienced personnel carry out paracentesis. (Hepatology 2004;40:484-488.)
Norepinephrine regulates hepatic innate immune system in leptin-deficient mice with nonalcoholic steatohepatitis
Authors: Li Zhiping , Oben Jude A. , Yang Shiqi , Lin Huizhi , Stafford Elizabeth A. , Soloski Mark J. , Thomas Steven A. , Diehl Anna Mae
Published: August 2004

It is not known why natural killer T (NKT) cells, which modulate liver injury by regulating local cytokine production, are reduced in leptin-deficient ob/ob mice. NKT cells express adrenoceptors. Thus, we hypothesize that the low norepinephrine (NE) activity of ob/ob mice promotes depletion of liver NKT cells, thereby sensitizing ob/ob livers to lipopolysaccharide (LPS) toxicity. To evaluate this hypothesis, hepatic NKT cells were quantified in wild-type mice before and after treatment with NE inhibitors, and in dopamine β-hydroxylase knockout mice (which cannot synthesize NE) and ob/ob mice before and after 4 weeks of NE supplementation. Decreasing NE activity consistently reduces liver NKT cells, while increasing NE has the opposite effect. Analysis of hepatic and thymic NKT cells in mice of different ages demonstrate an age-related accumulation of hepatic NKT cells in normal mice, while liver NKT cells become depleted after birth in ob/ob mice, which have increased apoptosis of hepatic NKT cells. NE treatment inhibits apoptosis and restores hepatic NKT cells. In ob/ob mice with reduced hepatic NKT cells, hepatic T and NKT cells produce excessive T helper (Th)-1 proinflammatory cytokines and the liver is sensitized to LPS toxicity. NE treatment decreases Th-1 cytokines, increases production of Th-2 cytokines, and reduces hepatotoxicity. Studies of CD1d-deficient mice, which lack the receptor required for NKT cell development, demonstrate that they are also unusually sensitive to LPS hepatotoxicity. In conclusion, low NE activity increases hepatic NKT cell apoptosis and depletes liver NKT cells, promoting proinflammatory polarization of hepatic cytokine production that sensitizes the liver to LPS toxicity. (Hepatology 2004;40:434-441.)
The Effects of Ursodeoxycholic Acid on Serum and Biliary Noncholesterol Sterols in Patients With Gallstones
Authors: Miettinen T E , Tarpila S , Gylling H
Published: August 2004

Litholytic bile acid ursodeoxycholic acid (UDCA) reduces biliary cholesterol secretion and alters cholesterol metabolism by mechanisms that are not fully understood. To evaluate cholesterol metabolism during UDCA treatment, we studied serum and biliary lipids and cholesterol precursor sterols (lanosterol and other dimethyl and monomethyl sterols, lathosterols, and desmosterol), indicators of cholesterol synthesis, and plant sterols campesterol and sitosterol, indicators of cholesterol absorption, before and during administration of UDCA, 9 mg/kg/d, for 26 weeks in eight patients with radiolucent gallstones. During UDCA administration, serum lipid concentrations were unchanged, but the biliary concentration and molar percentage of cholesterol were markedly decreased. The proportions of the cholesterol precursor sterols to cholesterol were significantly interrelated between serum and bile before and especially during UDCA administration. Lanosterol and lathosterol levels, especially in bile, were significantly decreased by 43% and 34%, suggesting that UDCA may inhibit cholesterol synthesis. Levels of the other methylated precursor sterols were increased in serum and bile. The esterification percentages of all sterols were unchanged. The plant sterol–to–cholesterol ratios increased significantly in serum and bile, and there was an inverse correlation between the increment of serum plant sterols and decreased biliary molar percentage of cholesterol. In conclusion, UDCA may inhibit cholesterol synthesis possibly at the squalene synthase or 4α–demethylase steps, resulting in decreased biliary secretion of cholesterol. Reduced biliary sterol secretion probably increased serum plant sterol levels, indicating that under these conditions they no longer reflect the intestinal efficiency of cholesterol absorption.
Effect of Albendazole on Recurrent and Residual Alveolar Echinococcosis of the Liver After Surgery
Authors: Ishizu H , Uchino J , Sato N , Aoki S , Suzuki K , Kuribayashi H
Published: August 2004

Patients with alveolar echinococcosis of the liver (AEL) can be cured by complete excision of the lesions; however, it is not always completely resectable in advanced cases. Recently, benzimidazole–type drugs have been reported to be effective in nonresectable AEL. One hundred fifty–two patients with AEL have been surgically treated in our institution since 1937. Our clinical trial with albendazole, one of the benzimidazole carbamates, has included 26 cases of AE since September 1988, each of whom had undergone an operation. Complete resection was performed in only six cases. Evaluation of response to the treatment was possible in 20 cases. A favorable response to albendazole, such as decreases in the size of the lesions, changes in cyst morphology, and amelioration in clinical symptoms or signs, was achieved in 11 (55%) cases. These favorable responses were also seen in cases of noncurative resection and palliative operation. The cumulative survival rate of the patients was 87%, 15 years after the operation. A complete response was achieved in one case; the residual lesion in the liver completely disappeared on the computed tomography image 3.5 years after noncurative surgery. Palliative or mass reduction surgery combined with albendazole therapy may be a strategy for advanced disease, especially when complete resection might result in significant morbidity or mortality.
Liver Cell Proliferation Induced by Nafenopin and Cyproterone Acetate Is Not Associated With Increases in Activation of Transcription Factors Nf–κB and Ap–1 or With Expression of Tumor Necrosis Factor α
Authors: Menegazzi M , Carcereri-De Prati A , Suzuki H , Shinozuka H , Pibiri M , Piga R , Columbano A , Ledda-Columbano G M
Published: August 2004

Our previous studies have shown a different pattern of immediate early gene and growth factor gene expression between compensatory liver regeneration occurring after cell loss/death and direct hyperplasia induced by primary mitogens. In the present study, modifications in the activation of two transcription factors, NF–κB and AP–1; steady– state levels of tumor necrosis factor α (TNF–α) messenger RNA (mRNA); and induction of the inducible nitric oxide synthase (iNOS) were examined in rat liver during different types of cell proliferation. Compensatory regeneration was induced in male Wistar rats by partial hepatectomy of two thirds (PH) or a necrogenic dose of CCl4 (2 mL/kg), whereas direct hyperplasia was induced by a single administration of the primary mitogens lead nitrate (LN, 100 micromol/kg), cyproterone acetate (CPA, 60 mg/kg), or nafenopin (NAF, 200 mg/kg). Liver regeneration after treatment with CCl4 was associated with an increase in steady–state levels of TNF–α mRNA, activation of NF–κB and AP–1, and induction of iNOS. A strong and prolonged activation of NF–κB but not of AP–1 was observed in LN–induced hyperplasia. LN also induced an increase in hepatic levels of TNF–α and iNOS mRNA. On the other hand, direct hyperplasia induced by two other primary mitogens, NAF and CPA, occurred in the complete absence of modifications in the hepatic levels of TNF–α mRNA, activation of NF–κB and AP–1, or induction of iNOS, although the number of hepatocytes entering S phase 18 to 24 hours after NAF was similar to that seen after PH. These results add further support to the hypothesis that cell proliferation occurring in the absence of cell loss/death may be triggered by unknown signaling pathways different from those responsible for the transition of hepatocytes from G0 to G1 after PH or cell necrosis.
Frequency of Mutation and Deletion of the Tumor Suppressor Gene Cdkn2a (Mts1/P16) in Hepatocellular Carcinoma From An Australian Population
Authors: Biden K , Young J , Buttenshaw R , Searle J , Cooksley G , Xu D B , Leggett B
Published: August 2004

The tumor suppressor gene CDKN2A (MTS1/p16), located on chromosome 9p21, is inactivated in a variety of tumors including melanomas and tumors of the biliary tract, pancreas, and stomach. The aim of the present study was to determine whether this gene is inactivated in hepatocellular carcinoma (HCC). Twenty–three primary HCCs and four HCC cell lines were examined. Loss of heterozygosity (LOH) analysis was performed using eight polymorphic markers immediately surrounding CDKN2A, and showed a contiguous region of loss, with the two most commonly deleted markers being D9S1604, located between the p16 and p15 genes, at which 7 of 13 informative tumors (54%) showed loss, and D9S171, with 4 of 14 LOH (29%). Exons 1, 2, and 3 of CDKN2A were amplified by polymerase chain reaction to detect homozygous deletions, and single–strand conformation polymorphism (SSCP) analysis was performed to screen for mutations. No homozygous deletions were detected in any sample. SSCP and sequence analysis showed the same nucleotide change at codon 148 in four tumors. This has been reported elsewhere as a polymorphism. One of these four tumors also contained a mutation at codon 119, resulting in the substitution of an acidic amino acid for a basic one. It is concluded that CDKN2A is infrequently deleted or mutated in HCC. The region of allelic loss upstream from CDKN2A might result in inactivation of regulatory sequences important in the expression of this gene; alternatively, a second tumor suppressor gene may be present in the region 9p21–22, proximal to CDKN2A. These possibilities require further investigation.