bluuebunny/crossref_metadata_2025 huggingface dataset:
Composing on Stage: Schoenberg and the Creative Process as Public Performance
Authors: Auner Joseph
Published: September 2005

Drawing on published and unpublished sources, this article traces the changing ways in which Schoenberg made his sketches, fragments, and the creative process in general integral aspects of both his identity as a composer and the reception of his music. One side of this story is Schoenberg's well-known concern for how posterity would view him, evident in his obsession with demonstrating his stature as a genius and defining his place in history as the first to break with tonality and as the inventor of "the method of composing with twelve tones related only to one another." But as significant for the present context are the ways that, beginning in the first decade of the century, he started to make his Nachlass known through the dissemination of manuscripts, sketches, and fragments, and by means of discussions of the creative process and compositional techniques in his voluminous writings. Schoenberg's interjection of the act of composition into public musical discourse has clear origins in the nineteenth century, but it also has important implications for the blurring of boundaries between the work, the creative process, the artist, and the audience, a characteristic of twentieth- and twenty-first-century art and now a fundamental feature of our cultural life.
Come See About Me: Enchantment of the Double in The Picture of Dorian Gray
Authors: CRAFT CHRISTOPHER
Published: September 2005

ABSTRACT Focusing upon the alienation-effects generated by technologies of duplication (portrait, mirror), this essay explores the enchantment of the double in Oscar Wilde's The Picture of Dorian Gray.
Obscuritas anddissimulatio in Cicero's pro Tullio
Authors: La Bua Giuseppe
Published: September 2005

Abstract In his commentary on Cicero,De inventione, Grillius gives Cicero'spro Tullio as an example of the genus obscurum causae and identifies the occultatio negotii as the distinction of this type of exordium. This article argues that the occultatio negotii is an ironic form ofdissimulatio, by which the orator hides the real object of the debate and clouds the issue, drawing the attention of the judges to points not directly connected with it. This oratorical tactic is used by Cicero in thepro Tullio. Avoiding the real issue (the clash between Tullius' and Fabius' slaves), the orator focuses on a juridical problem (the meaning ofdolus malus) and appears as a defender of thevoluntas legis, opposing the (supposed) legal formalism of the antagonist.
The Open Use of Living: Prudence, Decorum, and the ‘Square Man’
Authors: Pender Stephen
Published: September 2005

Abstract In the Nicomachean Ethics, Aristotle argues that a happy man is “foursquare beyond reproach” (τετράγωνοσ άνευ ψόγου or, in a common Latin translation, quadratus sine probro). To be foursquare, the happy man must bear the chances of life nobly and decorously as well as possess the qualities of the phronimos or good deliberator. That Aristotle moors felicity to prudence and decorum spurs classical, medieval, and early modern commentators, moral philosophers, and poets; by tracing the reception and use of the square man, I explore change and continuity in the relationship between prudence and decorum in some classical, late medieval, and early modern texts in order to suggest that prudent and practical persuasion emerges as a flexible responsive mode of perceiving ethical and political practice in the early modern period.
Three‐dimensional Total Synchronous Luminescence Spectroscopy Criteria for Discrimination Between Normal and Malignant Breast Tissues
Authors: Dramićanin Tatjana , Dramićanin Miroslav D. , Jokanović Vukoman , Nikolić‐Vukosavljević Dragica , Dimltrijević Bogomir
Published: September 2005

Specimens of malignant and normal female human breast tissues were analyzed after surgery by means of synchronous luminescence spectroscopy. Measurements were performed in the ranges of excitation wavelengths from 330 to 650 nm and synchronous wavelengths from 30 to 120 nm to obtain ordinary and first derivative three‐dimensional total synchronous luminescence spectra (3d‐TSLS) of each specimen. Arithmetic mean of these spectra has been calculated for normal and malignant specimens and analyzed to establish criteria for tissue differentiation. Spectral domain volumes (volumes below luminescence intensity surface) and mean spectral slopes have been calculated and also analyzed as tissue discrimination criteria. The obtained results are discussed in view of the possible relevance of synchronous luminescence spectroscopy in discrimination between normal and malignant breast tissue.
Limbal Epithelial Side-Population Cells Have Stem Cell–Like Properties, Including Quiescent State
Authors: Umemoto Terumasa , Yamato Masayuki , Nishida Kohji , Yang Joseph , Tano Yasuo , Okano Teruo
Published: September 2005

Corneal epithelial (CE) stem cells are believed to reside in the basal layer of the limbal epithelium but remain poorly understood due to the lack of an accepted in vivo reconstitution assay as well as definitive markers for epithelial stem cells. It has been reported that side-population (SP) cells with the ability to efflux the DNA-binding dye Hoechst 33342 have stem cell–like properties and that the SP phenotype accurately represents a quiescent and immature stem cell population in the adult bone marrow. In the present study, we investigated whether SP cells isolated from the limbal epithelium have stem cell–like properties. SP cells, separated by fluorescence-activated cell sorting, comprise approximately 0.4% of all limbal epithelial cells and have markedly higher expression of the stem cell markers ABCG2, Bmi-1, and nestin but no expression of markers for differentiated CE cells compared with non-SP cells. Cell-cycle and telomerase activity analyses revealed that SP cells are growth arrested and reside in the quiescent state. Moreover, limbal epithelial SP cells did not demonstrate proliferative capabilities under typical in vitro epithelial cell culture conditions using 3T3 feeder layers. These findings present the possibility that quiescent limbal epithelial SP cells may represent an extremely immature stem cell population compared with currently defined epithelial stem or progenitor cells.
Energy and variational principles for piles in dissipative soil
Authors: Einav I.
Published: September 2005

Energy and variational principles have provided a valuable tool to analyse the behaviour of elastic structures for quite a long time. They have also been used infrequently to study soil–pile interaction problems, following the traditional methods that were developed for elastic structures. One of the possible reasons for the gap in applications is that soil is not a non-dissipative elastic medium. This paper presents an alternative energy-based variational approach that does account for the inelastic dissipative nature of soils. Other than theoretical advantages, the new approach seems very promising for practical reasons. This approach allows the recovery of an inherent set of differential equations, which in particular cases of proportional monotonic loading conditions may become identical to the previous equations obtained from the ‘elasticity’ methods. The new method also allows modelling of the kinematic hardening nature of the soil during cyclic loading events.
Imaging heterogeneities with electrical impedance tomography: laboratory results
Authors: Borsic A. , Comina C. , Foti S. , Lancellotta R. , Musso G.
Published: September 2005

Electrical impedance tomography (EIT) is commonly used on site as a characterisation and monitoring tool. In the present work this technique has been applied at laboratory scale in order to investigate its capabilities in controlled conditions, with particular reference to the detection of anomalies in sandy samples. Various configurations have been studied, investigating heterogeneities due to variation of porosity, grain size distribution and clay content. The results show the great potential of EIT as an imaging tool in laboratory equipment to check sample homogeneity and to monitor processes during tests.
A three-dimensional upper-bound approach to slope stability analysis based on RFEM
Authors: Chen J. , Yin J. -H. , Lee C. F.
Published: September 2005

An upper-bound limit analysis method based on rigid finite elements has been developed recently. Numerical procedures for implementing the three-dimensional upper-bound slope stability analysis using rigid finite elements are presented in the paper. The search for the minimum value of the factor of safety can be set up as a non-linear programming problem. Because of the existence of non-linear equalities, a special sequential quadratic programming (SQP) algorithm, CFSQP, is applied to obtain the optimal solution in the paper. Two test problems are used to examine the validation and capability of the present rigid element upper-bound limit analysis method by comparison with results obtained by other methods. A practical example illustrates the application of the present method in three-dimensional slope stability analysis.
Field simulation of in situ water content and temperature changes due to ground–atmospheric interactions
Authors: Cui Y. J. , Lu Y. F. , Delage P. , Riffard M.
Published: September 2005

A site in Boissy-le-Chatel, France, has been instrumented with a meteorological station, piezometers, thermocouples and time domain reflectometry equipment, in order to monitor solar radiation energy, precipitation, runoff, wind speed, air temperature, air humidity, soil temperature, soil volumetric water content, and underground water table levels. Data recorded in April 1999 were used to validate predictions of soil water content changes based on the works of Blight and Wilson et al. In the elaborated approach, Penman's equation is employed to evaluate the potential evapotranspiration, and Darcy and Fick's laws are used to describe the flows of liquid and vapour water respectively. The soil water content and hydraulic conductivity are presumed to be functions of soil suction, and the coefficient of latent heat of vaporisation of water is assumed to be a linear function of temperature. The formula proposed by De Vries is used for calculation of the thermal conductivity coefficient. The results of Wilson et al. for laboratory conditions were used to validate the model used. To simulate field conditions, climatic data were used to calculate the volumetric water content and temperature profiles in the soil, and the calculated values were compared with direct measurements. Satisfactory results were obtained.
Broiler Diet Modification and Litter Storage
Authors: McGrath Joshua M. , Sims J. Thomas , Maguire Rory O. , Saylor William W. , Angel C. Roselina , Turner Benjamin L.
Published: September 2005

Modifying broiler diets to mitigate water quality concerns linked to excess phosphorus (P) in regions of intensive broiler production has recently increased. Our goals were to evaluate the effects of dietary modification, using phytase and reduced non‐phytate phosphorus (NPP) supplementation, on P speciation in broiler litters, changes in litter P forms during long‐term storage, and subsequent impacts of diets on P in runoff from litter‐amended soils. Four diets containing two levels of NPP with and without phytase were fed to broilers in a three‐flock floor pen study. After removal of the third flock, litters were stored for 440 d at their initial moisture content (MC; 24%) and at a MC of 40%. Litter P fractions and orthophosphate and phytate P concentrations were determined before and after storage. After storage, litters were incorporated with a sandy and silt loam and simulated rainfall was applied. Phytase and reduced dietary NPP significantly reduced litter total P. Reducing dietary NPP decreased water‐extractable inorganic phosphorus (IP) and the addition of dietary phytase reduced NaOH‐ and HCl‐extractable organic P in litter, which correlated well with orthophosphate and phytic acid measured by 31P nuclear magnetic resonance (NMR), respectively. Although dry storage caused little change in P speciation, wet storage increased concentrations of water‐soluble IP, which increased reactive P in runoff from litter‐amended soils. Therefore, diet modification with phytase and reduced NPP could be effective in reducing P additions on a watershed scale. Moreover, efforts to minimize litter MC during storage may reduce the potential for dissolved P losses in runoff.
Predicted Impact and Evaluation of North Carolina's Phosphorus Indexing Tool
Authors: Johnson Amy M. , Osmond Deanna L. , Hodges Steven C.
Published: September 2005

Increased concern about potential losses of phosphorus (P) from agricultural fields receiving animal waste has resulted in the implementation of new state and federal regulations related to nutrient management. In response to strengthened nutrient management standards that require consideration of P, North Carolina has developed a site‐specific P indexing system called the Phosphorus Loss Assessment Tool (PLAT) to predict relative amounts of potential P loss from agricultural fields. The purpose of this study was to apply the PLAT index on farms throughout North Carolina in an attempt to predict the percentage and types of farms that will be forced to change management practices due to implementation of new regulations. Sites from all 100 counties were sampled, with the number of samples taken from each county depending on the proportion of the state's agricultural land that occurs in that county. Results showed that approximately 8% of producers in the state will be required to apply animal waste or inorganic fertilizer on a P rather than nitrogen basis, with the percentage increasing for farmers who apply animal waste (approximately 27%). The PLAT index predicted the greatest amounts of P loss from sites in the Coastal Plain region of North Carolina and from sites receiving poultry waste. Loss of dissolved P through surface runoff tended to be greater than other loss pathways and presents an area of concern as no best management practices (BMPs) currently exist for the reduction of in‐field dissolved P. The PLAT index predicted the areas in the state that are known to be disproportionately vulnerable to P loss due to histories of high P applications, high densities of animal units, or soil type and landscapes that are most susceptible to P loss.
Hybrid Periodic Mesoporous Organosilicas
Authors: Whitnall W. , Asefa T. , Ozin G. A.
Published: September 2005

In this study we report the synthesis of a new class of materials called hybrid periodic mesoporous organosilicas (HPMOs). By coupling a silsesquioxane precursor through at least two chemical linkages to the mesopore walls of a pre‐existing periodic mesoporous silica (PMS) or periodic mesoporous organosilica (PMO). Many of the problems of a conventional PMO material can be avoided while ensuring efficient use of the bridging organic functional groups of the silsesquioxane. We demonstrate this concept for PMS by anchoring various silsesquioxanes, such as ethene and ethane silsesquioxanes, to the mesopore walls of the PMS. The addition of anchored silsesquioxane monolayers and multilayers to the mesopore walls also allows for the strict control of the diameter of the mesopore as well as the mesopore wall thickness in the final HPMO material. Additionally it is shown that having the silsesquioxane located solely on the surface of the mesopores in HPMOs gives increased chemical accessibility of the organic bridge‐bonded moiety when compared with their PMO counterparts containing the bridge‐bonded organic both on the surface and within the pore walls.
Rate constants of mass transfer kinetics in reversed phase liquid chromatography
Authors: Hong Lan , Gritti Fabrice , Gulochon Georges , Kaczmarski Krzysztof
Published: September 2005

The parameters of the kinetics of mass transfer of several n‐alkylbenzenes were measured by the method of moments on a series of columns prepared with different samples of the same RPLC packing material having widely different average particle diameters, from 3 to 50 μm. These data were analyzed using the available models, and correlations. The best agreement between experimental and theoretical data was obtained under the assumption that the rate constant for the external mass transfer increases with increasing average particle size, an unexpected conclusion. It was also shown that the interpretation of the relative importance of the roles of pore diffusivity and surface diffusivity in the internal mass transfer kinetics is somewhat ambiguous and that the conclusion to be drawn from experimental results depends on the assumptions made regarding the tortuosity model and the relationship between k
ext and the average particle size. © 2005 American Institute of Chemical Engineers AIChE J, 2005
Experimental and numerical investigation of particle transport in a horizontal pipe
Authors: Rundqvist Robert , Ljus Camilla , van Wachem Berend
Published: September 2005

Measurements were made of the concentration of particles in a horizontal transport pipe using an optical probe. The distribution of particles over the pipe cross‐section was measured. Particle transport in a horizontal two‐dimensional (2‐D) channel was simulated using an Eulerian two‐fluid model. A model is proposed for the turbulent dispersion of particles and implemented in the two‐fluid model. The turbulence in the gas phase is modeled using a modified k − ϵ model that accounts for the influence of the particles on the gas‐phase turbulence. Comparisons with measurements of air‐particle flow in a horizontal pipe show qualitative agreement between measurements and calculations. © 2005 American Institute of Chemical Engineers AIChE J, 2005
A quasi‐sequential approach to large‐scale dynamic optimization problems
Authors: Hong Weirong , Wang Shuqing , Li Pu , Wozny Günter , Biegler Lorenz T.
Published: September 2005

A novel sequential approach for solving dynamic optimization problems containing path constraints on state variables is presented and its performance analyzed. As in the simultaneous approach, we discretize both state and control variables using collocation on finite elements, so that path constraints can be guaranteed inside each element. The state variables are solved in a manner similar to that in the sequential approach; this eliminates the discretized differential‐algebraic equations and state variables, so that the problem is reduced to a smaller problem only with inequality constraints and control variables. Therefore, it possesses advantages of both the simultaneous and the sequential approach. Furthermore, the elimination of the equality constraints substantially simplifies the line search problem and thus larger steps can be taken by successive quadratic programming (SQP) toward the optimum. We call this dynamic optimization method a quasi‐sequential approach. We compare this new approach with the simultaneous approach in terms of computational cost and by analyzing the solution path. A highly nonlinear reactor control and the optimal operation of a heat‐integrated column system are used to demonstrate the effectiveness of this approach. As a result, it can be concluded that this quasi‐sequential approach is well suited for solving highly nonlinear large‐scale optimal control problems. © 2005 American Institute of Chemical Engineers AIChE J, 2006
Notified cases of occupational asthma in Norway: Exposure and consequences for health and income
Authors: Leira Håkon Lasse , Bratt Unni , Slåstad Siri
Published: September 2005

Background

Estimates of occupational asthma (OA) may vary between countries and within countries. An overview of cases of occupational asthma in Norway has not been presented previously. Norwegian physicians are obliged to report occupational diseases to the Labor Inspection Authority. The registry of these notifications was used to study the cases of OA.

Methods

Data were collected from the notifications for respiratory disease for the period 1995–1999. A postal questionnaire inquiring into work, respiratory symptoms, smoking, and socioeconomic consequences of the disease was sent to 1,239 workers with a physician's diagnosis of obstructive respiratory disease.

Results

The response rate to the questionnaire was 81% (1,000 workers of whom 723 had OA). On an average, 223 annual cases of OA were reported in the study period (1995–1999). The highest incidence of notifications was found in the primary aluminum industry and in bakers, car painters, and welders. At the time of notification, more than half of the workers had left their original jobs. At the time of this study 2–6 years later, approximately the same proportion of workers had experienced a reduction in income and had received financial compensation; 60–78% were still on antiasthmatic medication.

Discussion

The notification of OA by Norwegian physicians may underestimate the true incidence considerably. A majority of the notified cases seemed to become chronic despite medical treatment.

Conclusions

More emphasis should be put on early recognition of OA and on the reduction or cessation of exposure after the diagnosis of OA. Am. J. Ind. Med. 2005. © 2005 Wiley‐Liss, Inc.
Das Ubiquitinsystem im Proteinabbau und einige seiner Aufgaben bei der Steuerung des Zellteilungszyklus (Nobel‐Vortrag)
Authors: Hershko Avram
Published: September 2005

Der Proteinabbau ist ein genaustens gesteuerter Prozess, bei dem das Eiweißmolekül Ubiquitin eine entscheidende Rolle spielt, indem es an Proteine bindet und sie für ihren Abbau markiert. Die zellulären Mechanismen dieses Vorgangs sind heute dank der Arbeiten der Chemienobelpreisträger 2004, Irwin Rose, Avram Hershko und Aaron Ciechanover (Fotos, von links), weitgehend bekannt. In ihren Nobelvorträgen berichten die Laureaten aus erster Hand.
Managing invasive carp (Cyprinus carpio L.) for habitat enhancement at Botany Wetlands, Australia
Authors: Pinto L. , Chandrasena N. , Pera J. , Hawkins P. , Eccles D. , Sim R.
Published: September 2005

In Australia, the carp Cyprinus carpio L. is regarded as a threat to the native fish and the aquatic environment. In recent years, Botany Wetlands, a significant coastal wetland in the Sydney region, has been invaded by the undesirable cyprinids, carp and goldfish (Carrasius auratus L.).

In 1996 a cyprinid removal programme commenced at Botany Wetlands with the objective of managing the invasive species, increasing fish diversity, reducing cyanobacterial blooms and hence enhancing the aquatic habitat. Using electrofishing and gill netting, 4073 carp and 261 goldfish, amounting to 10 117 kg of cyprinid biomass were removed between 1996 and 2004. The captured carp ranged from 60 to 835 mm. Males matured before females. Carp between 350 and 680 mm in length grew at the rate of 1.66±0.38 g day−1.

The success of the programme was monitored by assessing four indicators related to carp populations and two related to habitat. The former included the pattern of length–frequency distribution, mean weight per size class, condition factor (CF) and the catch per unit effort (CPUE), and the latter the Secchi disc transparency and cyanobacterial counts. After 8 yr of removal, the plots of carp length–frequency distribution flattened, CF decreased from 2.86 to 1.82 and CPUE decreased from 97 kg day−1 to 50 kg day−1. A 10‐fold decrease occurred in cyanobacterial counts and the Secchi disc transparency increased by 20%. More than 20 000 fingerlings of native Australian bass Macquaria novemaculeata (S.) have been introduced to the wetlands, increasing the potential for juvenile carp predation and biodiversity.

Copyright © 2005 John Wiley & Sons, Ltd.
DHRAM: a method for classifying river flow regime alterations for the EC Water Framework Directive
Authors: Black A.R. , Rowan J.S. , Duck R.W. , Bragg O.M. , Clelland B.E.
Published: September 2005

A method has been developed for assessing the degree of human alteration of river flow regimes relative to near‐natural or reference conditions.

The Dundee Hydrological Regime Alteration Method (DHRAM) utilizes the Indicators of Hydrologic Alteration approach of the US Nature Conservancy to classify the risk of damage to in‐stream ecology using a five‐class scheme compatible with the requirements of the EC Water Framework Directive.

Separate methods have been developed for rivers and lakes, though only the former are considered in this paper.

DHRAM uses daily mean flow time‐series data, representing un‐impacted and impacted situations for the site of interest, in relation to any type of anthropogenic hydrological impact such as impoundments, abstractions or flow augmentation.

Procedures for coping with different levels of data availability are outlined, utilizing the Micro Low Flows computer package to generate synthetic series of daily mean flows, supplemented by flow alteration data as appropriate.

The utility of DHRAM is demonstrated through a pair of Scottish case studies illustrating its ability in classifying regime alteration and supporting mapping, which will be of value to river basin managers.

Finally, present and future issues relating to the calibration of DHRAM scores to levels of ecological damage are discussed.

Copyright © 2005 John Wiley & Sons, Ltd.
Distribution of caspase‐14 in epidermis and hair follicles is evolutionarily conserved among mammals
Authors: Alibardi Lorenzo , Tschachler Erwin , Eckhart Leopold
Published: September 2005

Caspase‐14, a member of the caspase family of cysteine proteases, is almost exclusively expressed in the epidermis. Studies on human and mouse cells and tissues have implicated caspase‐14 in terminal differentiation of epidermal keratinocytes and in the formation of the stratum corneum. Here we investigated evolutionary aspects of the role of caspase‐14 by analyzing its distribution in the epidermis and hair follicles of representative species of placental mammals, marsupials, and monotremes. Immunocytochemical staining showed that caspase‐14 is consistently expressed in the granular and corneous layer of the epidermis of all mammalian species investigated. Ultrastructural analysis using gold‐labeled anticaspase‐14 antibodies revealed that caspase‐14 is associated preferentially with keratin bundles and amorphous material of keratohyalin granules, but is also present in nuclei of transitional cells of the granular layer and in corneocytes. In hair follicles, caspase‐14 was diffusely present in cornifying cells of the outer root sheath, in the companion layer, and, most abundantly, in the inner root sheath of all mammalian species here analyzed. In Henle and Huxley layers of the inner root sheath, labeling was seen in nuclei and, more diffusely, among trichohyalin granules of cornifying cells. In summary, the tissue expression pattern and the intracellular localization of caspase‐14 are highly conserved among diverse mammalian species, suggesting that this enzyme is involved in a molecular process that appeared early in the evolution of mammalian skin. The association of caspase‐14 with keratohyalin and trichohyalin granules may indicate a specific role of caspase‐14 in the maturation of these keratinocyte‐specific structures. © 2005 Wiley‐Liss, Inc.
Different levels of the neuronal nitric oxide synthase isoform modulate the rate of osteoclastic differentiation of TIB‐71 and CRL‐2278 RAW 264.7 murine cell clones
Authors: Nicolin Vanessa , Ponti Cristina , Narducci Paola , Grill Vittorio , Bortul Roberta , Zweyer Marina , Vaccarezza Mauro , Zauli Giorgio
Published: September 2005

It has been clearly established that osteoclasts, which play a crucial role in bone resorption, differentiate from hematopoietic cells belonging to the monocyte/macrophage lineage in the presence of macrophage‐colony stimulating factor (M‐CSF) and receptor activator of NF‐κB ligand (RANKL). We have here investigated the M‐CSF‐ and RANKL‐induced osteoclastic differentiation of two distinct clones of the murine monocytic/macrophagic RAW 264.7 cell line, known as TIB‐71 and CRL‐2278, the latter cell clone being defective for the expression of the inducible nitric oxide synthase isoform in response to interferon‐γ or lipopolysaccharide. CRL‐2278 cells demonstrated a more rapid osteoclastic differentiation than TIB‐71 cells, as documented by morphology, tartrate‐resistant acid phosphatase positivity, and bone resorption activity. The enhanced osteoclastic differentiation of CRL‐2278 was accompanied by a higher rate of cells in the S/G2‐M phases of cell cycle as compared to TIB‐71. The analysis of nitric oxide synthase (NOS) isoforms clearly demonstrated that only neuronal NOS was detectable at high levels in CRL‐2278 but not in TIB cells under all tested conditions. Moreover, the broad inhibitor of NOS activity L‐NAME significantly inhibited osteoclastic differentiation of CRL‐2278 cells. Altogether, these results demonstrate that a basal constitutive neuronal NOS activity positively affects the RANKL/M‐CSF‐related osteoclastic differentiation. © 2005 Wiley‐Liss, Inc.
Angioarchitecture of the rabbit extrahepatic bile ducts and gallbladder
Authors: Jackowiak Hanna , Lametschwandtner Alois
Published: September 2005

The angioarchitecture of extrahepatic bile ducts and gallbladder of the miniature rabbit was studied by scanning electron microscopy (SEM) of vascular corrosion casts. Light microscopy of Masson‐stained, paraffin‐embedded transverse tissue sections served to attribute cast vascular structures to defined layers of bile ducts and gallbladder. In all segments of the bile tract, a mucosal and a subserosal vascular network was found. In glandular segments, the mucosal network was composed of a meshwork of subepithelial and circumglandular capillaries, which serve the mucosal functions. Differences in the angioarchitectonic patterns existed only in the subserosal networks as hepatic ducts own one supplying arteriole only, while the common bile duct owns a well‐defined rete arteriosum subserosum. A well‐developed dense subserosus venous plexus was present throughout the bile tract. Vascular patterns of the gallbladder body resembled those of the bile duct, whereby the dense subserous venous plexus was located close to the mucosal capillary network. The subserosal network in the neck of the gallbladder resembled that of the cystic duct. Spatial changes of the mucosal vascular network during volume changes of the gallbladder were documented. Measurements from tissue sections revealed bile tract diameters of 220–400 μm (extrahepatic ducts), 500–650 μm (cystic duct), and 4–6 mm (common bile duct). Data gained from high‐powered SEM micrographs of vascular corrosion casts revealed vessel diameters of 200 μm (cystic artery), 90–110 μm (cystic vein), 30–40 μm (feeding arterioles), and 25–110 μm (subserosal venules). Crypt diameters in the filled gallbladder were 300–1,500 μm; those in the contracted organ were 100–600 μm. © 2005 Wiley‐Liss, Inc.
Total Synthesis and Further Scrutiny of the in vitro Antifungal Activity of 6‐Nonadecynoic Acid
Authors: Carballeira Néstor M. , Sanabria David , Parang Keykavous
Published: September 2005

The antifungal, naturally occurring acetylenic fatty acid 6‐nonadecynoic acid was synthesized in three steps (18 % overall yield), for the first time starting with commercially available 1‐tetradecyne. The synthesis developed herein will facilitate the further study of the antifungal properties of this naturally occurring acetylenic fatty acid. The 6‐nonadecynoic acid exhibited the best antifungal activity (< 4.3 μM) against Cryptococcus neoformans ATCC 66031 in Sabouraud Dextrose Broth (SDB) media. In our hands, it was not active against Candida albicans ATCC 14053 and Candida albicans ATCC 60193.
Incidence and risk factors of thromboembolism in systemic lupus erythematosus: A comparison of three ethnic groups
Authors: Mok Chi Chiu , Tang Sandy Shuk Kuen , To Chi Hung , Petri Michelle
Published: September 2005

Objective

To compare the incidence and risk factors for thromboembolic events in systemic lupus erythematosus (SLE) patients of different ethnic backgrounds.

Methods

SLE patients who were newly diagnosed or were referred within 6 months of diagnosis between 1996 and 2002 were prospectively followed up for the occurrence of thromboembolic events. Cumulative hazard and risk factors for thromboembolism were evaluated and compared among patients of different ethnic origins.

Results

We studied 625 patients who fulfilled the American College of Rheumatology criteria for SLE (89% women): 258 Chinese, 140 African Americans, and 227 Caucasians. The mean ± SD age at SLE diagnosis was 35.7 ± 14 years. After a followup of 3,094 patient‐years, 48 arterial events and 40 venous events occurred in 83 patients. The overall incidence of arterial and venous thromboembolism was 16/1,000 patient‐years and 13/1,000 patient‐years, respectively. The cumulative hazard of arterial events at 60 months after the diagnosis of SLE was 8.5%, 8.1%, and 5.1% for the Chinese, African Americans, and Caucasians, respectively. The corresponding cumulative risk of venous events was 3.7%, 6.6%, and 10.3%, respectively (P = 0.008 for Chinese versus Caucasians, by log rank test). Smoking, obesity, antiphospholipid antibodies, and use of antimalarial agents and exogenous estrogens were less frequent in the Chinese patients. In Cox regression models, low levels of high‐density lipoprotein (HDL) cholesterol, Chinese ethnicity, oral ulcers, and serositis predicted arterial events, whereas male sex, low levels of HDL cholesterol, antiphospholipid antibodies, non‐Chinese ethnicity, obesity, renal disease, and hemolytic anemia predicted venous events.

Conclusion

There are ethnic differences in the incidence of arterial and venous thromboembolism in patients with SLE that cannot be fully explained by the clinical factors studied. Further evaluation of other genetic and immunologic factors is warranted.
Knee stabilization in patients with medial compartment knee osteoarthritis
Authors: Lewek Michael D. , Ramsey Dan K. , Snyder‐Mackler Lynn , Rudolph Katherine S.
Published: September 2005

Objective

Individuals with medial knee osteoarthritis (OA) experience knee laxity and instability. Strategies aimed at muscle stabilization may influence the long‐term integrity of the joint. This study sought to determine how individuals with medial knee OA respond to a rapid valgus knee movement, to investigate the relationship between muscle‐stabilization strategies and knee instability.

Methods

Twenty‐one subjects with medial knee OA and genu varum and 19 control subjects were tested. Subjects stood with the test limb on a movable platform, comprising a plate that translated laterally to rapidly stress the knee's medial periarticular structures and create a potentially destabilizing sensation at the knee joint. Knee motion and muscle responses were recorded. Subjects rated the condition of their knee with a self‐report questionnaire about knee instability during daily activities.

Results

Prior to plate movement, the OA subjects demonstrated more medial muscle co‐contraction than did controls (P= 0.014). Following plate movement, the OA subjects shifted less weight off the test limb (P = 0.013) and had greater medial co‐contraction (P = 0.037). OA subjects without knee instability had higher co‐contraction of the vastus medialis medial hamstrings than did those who reported having instability that affected their daily activities (P = 0.038). More knee stability correlated positively with higher co‐contraction of the vastus medialis medial hamstrings prior to plate movement (r = 0.459, P = 0.042).

Conclusion

Individuals with medial knee OA attempt to stabilize the knee with greater co‐contraction of the medial muscle in response to laxity that appears on the medial side of the joint only. This strategy presumably contributes to higher joint compression and could exacerbate joint destruction, and therefore needs to be altered to slow or stop the progression of the OA disease process.
Development of a standardized method of assessment of radiographs and radiographic change in juvenile idiopathic arthritis: Introduction of the Dijkstra composite score
Authors: van Rossum Marion A. J. , Boers Maarten , Zwinderman Aeilko H. , van Soesbergen Renée M. , Wieringa Helen , Fiselier Theo J. W. , Franssen Marcel J. A. M. , Cate Rebecca ten , van Suijlekom‐Smit Lisette W. A. , Wulffraat Nico M. , van Luijk Wilma H. J. , Oostveen Johanna C. M. , Kuis Wietse , Dijkmans Ben A. C.
Published: September 2005

Objective

To evaluate the sensitivity to change of a newly developed radiologic assessment tool, the Dijkstra score, and to develop a numeric composite score and progressor classification scheme to apply in juvenile idiopathic arthritis (JIA) trials.

Methods

A placebo‐controlled trial of sulfasalazine (SSZ) in patients with oligoarticular‐ and polyarticular‐onset JIA yielded the data for this study. Data were obtained from 418 sets of radiographs of the clinically involved and contralateral joints (at study entry and at 6 months' followup) from 66 JIA patients. The Dijkstra score assesses the presence or absence of swelling, osteopenia, joint space narrowing, growth abnormalities, subchondral bone cysts, erosions, and malalignment. These signs were combined in the Dijkstra composite score, to assess inflammation (DI), growth (DG), and damage (DD). Progression was defined as an increase in either the DG or the DD score. Scores were evaluated among all radiographs, a standard set of films (hand, foot, and knee), and per patient. All scores were used to explore differences between the 2 treatment groups.

Results

Over time, 58% of joints remained normal, 23% remained abnormal but stable, 14% showed an increase in signs, and 5% showed a decrease in signs. Of the 66 JIA patients, 12% had normal radiographic findings throughout followup, 27% showed abnormalities at some sites without change, and 61% showed change in at least 1 site. Changes in the DI, DG, and DD scores varied considerably per type of joint and occurred most frequently in joints of the standard set. DI and DG scores changed most often in the knees, while DD scores changed primarily in the hands and feet. The disease course in 8% of joints was classified as progressive. Films of SSZ‐treated patients, versus the placebo group, showed less deterioration by the DD scores (P = 0.04), and the disease course was more often classified as nonprogressive in the SSZ group (P = 0.037). When progressors were defined as those who had at least one radiograph showing progression, significantly more placebo‐treated patients were considered progressors (P = 0.046).

Conclusion

In this trial data set, the Dijkstra composite score and the resulting progressor classification system are comprehensive and feasible tools that are sensitive to change and discriminate between clinical situations. They should now be tested by other investigators and in other data sets.
Dehydroascorbate transport in human chondrocytes is regulated by hypoxia and is a physiologically relevant source of ascorbic acid in the joint
Authors: McNulty Amy L. , Stabler Thomas V. , Vail Thomas P. , McDaniel Gary E. , Kraus Virginia B.
Published: September 2005

Objective

To evaluate the dehydroascorbate (DHA) transport mechanisms in human chondrocytes.

Methods

The transport of L‐14C‐DHA in human chondrocytes was analyzed under various conditions, including the use of RNA interference (RNAi), to determine the role of glucose transporter 1 (GLUT‐1) and GLUT‐3 in L‐14C‐DHA transport and to evaluate the effects of physiologically relevant oxygen tensions on L‐14C‐DHA transport. In order to estimate the contributions of reduced ascorbic acid (AA) and DHA to intracellular ascorbic acid (Asc), the quantities of AA and DHA were measured in synovial fluid samples from osteoarthritis (OA) patients and compared with the reported levels in rheumatoid arthritis (RA) patients.

Results

DHA transport in human chondrocytes was glucose‐sensitive, temperature‐dependent, cytochalasin B–inhibitable, modestly stereoselective for L‐DHA, and up‐regulated by low oxygen tension. Based on the RNAi results, GLUT‐1 mediated, at least in part, the uptake of DHA, whereas GLUT‐3 had a minimal effect on DHA transport. DHA constituted a mean 8% of the total Asc in the synovial fluid of OA joints, in contrast to 80% of the reported total Asc in RA joints.

Conclusion

We provide the first evidence that chondrocytes transport DHA via the GLUTs and that this transport mechanism is modestly selective for L‐DHA. In the setting of up‐regulated DHA transport at low oxygen tensions, DHA would contribute 26% of the total intracellular Asc in OA chondrocytes and 94% of that in RA chondrocytes. These results demonstrate that DHA is a physiologically relevant source of Asc for chondrocytes, particularly in the setting of an inflammatory arthritis, such as RA.
Disruption of the interaction of T cells with antigen‐presenting cells by the active leflunomide metabolite teriflunomide: Involvement of impaired integrin activation and immunologic synapse formation
Authors: Zeyda Maximilian , Poglitsch Marko , Geyeregger René , Smolen Josef S. , Zlabinger Gerhard J. , Hörl Walter H. , Waldhäusl Werner , Stulnig Thomas M. , Säemann Marcus D.
Published: September 2005

Objective

Leflunomide, a potent disease‐modifying antirheumatic drug of the isoxazole class, exhibits antiinflammatory, antiproliferative, and immunosuppressive effects by largely unknown mechanisms, although alterations of pyrimidine synthesis have been proposed. Successful immune responsiveness requires T cell activation by interaction with antigen‐presenting cells (APCs), and integrin activation and formation of an immunologic synapse (IS). In this study, we evaluated the impact of the active leflunomide metabolite teriflunomide on T cell integrin activation, evolution of the IS, and antigen‐specific formation of stable T cell/APC conjugates.

Methods

Effects of pharmacologic concentrations of teriflunomide on CD3/CD28‐ and lymphocyte function–associated antigen 1–induced signal transduction and activation of primary human T cells were investigated. Furthermore, T cells were stimulated with superantigen‐ and antigen‐pulsed APCs to study relocalization of molecules to the IS and T cell/APC conjugate formation.

Results

Teriflunomide inhibited T cell receptor (TCR)/CD3–mediated calcium mobilization, but other critical T cell signaling events, including activation of MAPK and NF‐κB, remained unaltered. In contrast, inhibition of TCR/CD3‐triggered β1,2 integrin avidity and integrin‐mediated costimulation (outside‐in signaling) by teriflunomide revealed a striking interference with integrin function that was independent of altered pyrimidine synthesis. Moreover, teriflunomide abolished molecule relocalization to the IS and induction of T cell/APC conjugates.

Conclusion

These data show that the active metabolite of leflunomide prevents the interaction of T cells with APCs to form an IS. Since IS formation is crucial for eliciting an immune response, this novel mechanism could underlie the beneficial effects of leflunomide in immune‐mediated disorders such as rheumatoid arthritis.
Maternal HLA class II compatibility in men with systemic lupus erythematosus
Authors: Stevens Anne M. , Tsao Betty P. , Hahn Bevra H. , Guthrie Katherine , Lambert Nathalie C. , Porter Allison J. , Tylee Tracy S. , Nelson J. Lee
Published: September 2005

Objective

Maternal–fetal cell transfer during pregnancy can lead to long‐lasting microchimerism, which raises the question of whether microchimerism sometimes contributes to autoimmune disease later in life. In an experimental model, transfusion of parental lymphocytes homozygous for major histocompatibility complex alleles results in systemic lupus erythematosus (SLE). We identified male patients with SLE and healthy male subjects and their mothers in order to investigate the mother–son HLA relationship in SLE risk. Male subjects were selected in order to avoid confounding due to fetal microchimerism, which may occur in women.

Methods

HLA genotyping for DRB1, DQA1, and DQB1 was conducted for sons and their mothers. Thirty men with SLE and their mothers were compared with 76 healthy men and their mothers.

Results

Sons with SLE were HLA‐identical with their mothers (bidirectionally compatible) for the basic HLA–DRB1 groups encoded by DRB1*01 through DRB1*14 more often than were healthy sons (odds ratio [OR] 5.0, P = 0.006). Each DRB1 group contains multiple allelic variants; male patients with SLE and their mothers often were identical for both DRB1 allelic variants (OR 3.2, P = 0.08). For DQA1 and DQB1, the ORs were 2.3 (P = 0.08) and 2.0 (P = 0.21), respectively. When analysis was limited to male subjects with SLE‐associated HLA genes (encoding HLA–DR2 or HLA–DR3), the differences further increased for DRB1 basic groups (OR 7.2, P = 0.01), DRB1 alleles (OR 15.0, P = 0.018), DQA1 6.4 (P = 0.006), and DQB1 (OR 5.7, P = 0.027). No increase in (unidirectional) compatibility of the mother from the son's perspective was observed at any locus.

Conclusion

We observed increased bidirectional HLA class II compatibility of male SLE patients and their mothers compared with healthy men and their mothers. This observation implies that maternal microchimerism could sometimes be involved in SLE and therefore merits further investigation.
Is the disease course of rheumatoid arthritis becoming milder?: Time trends since 1985 in an inception cohort of early rheumatoid arthritis
Authors: Welsing Paco M. J. , Fransen Jaap , van Riel Piet L. C. M.
Published: September 2005

Objective

Based on comparisons of short‐term cohort studies or cross‐sectional samples of patients from different calendar times, it has been suggested that present patients with rheumatoid arthritis (RA) have a milder disease course compared with that of patients in past decades. This study was undertaken to investigate whether the course of disease activity and functional disability in patients with RA has become milder over the past several years.

Methods

We used the Nijmegen inception cohort of early RA, which included all patients with newly diagnosed RA who had attended the department of rheumatology at Radboud University Nijmegen Medical Centre since 1985. Patients were assessed for disease activity by the Disease Activity Score in 28 joints (DAS28) every 3 months and for functional disability by the Health Assessment Questionnaire (HAQ) disability index (DI) every 6 months. Within the total cohort, 4 subcohorts were defined, based on the date of inclusion of the patients (1985–1990, 1990–1995, 1995–2000, 2000–2005). To investigate whether the course of disease activity and functional disability (over time) was different between the subcohorts, longitudinal regression analysis (linear mixed models) was used, with the DAS28 and HAQ DI over time as outcome variables, respectively, and subcohort as the independent variable, correcting for baseline demographic and clinical characteristics. The treatment strategy was compared between the subcohorts.

Results

The DAS28 at baseline and over the first 5 years of disease was lower in the more recent subcohorts. The HAQ DI did not show improvement but instead a trend toward worsening functional disability. Using longitudinal regression it was shown that disease activity improved early in the disease course and stabilized thereafter, and that this improvement was greater in patients in the more recent subcohorts and in patients with a higher baseline DAS28. Initially, the HAQ DI also improved but stabilized thereafter, and this initial improvement was less pronounced in patients in the more recent subcohorts and was greater for patients with a higher baseline HAQ DI. The treatment strategy was more aggressive in the more recent subcohorts, as shown by a shorter duration from diagnosis to the start of treatment with prednisone or disease‐modifying antirheumatic drugs (DMARDs), and a greater prevalence of DMARD therapy.

Conclusion

The course of disease activity in RA patients has become milder in more recent years. The reason for this improving trend remains to be elucidated, although the trend coincides with a more aggressive treatment strategy.