bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of markers for the selection of patients undergoing renal cell carcinoma‐specific immunotherapy
Authors: Seliger Barbara , Menig Matthias , Lichtenfels Rudolf , Atkins Derek , Bukur Jürgen , Halder Thomas M. , Kersten Michael , Harder Alois , Ackermann Angelika , Beck Joachim , Muehlenweg Bernd , Brenner Walburgis , Melchior Sebastian , Kellner Roland , Lottspeich Friedrich
Published: June 2003

Renal cell carcinoma (RCC) represents the most common malignant tumor in the kidney and is resistant to conventional therapies. The diagnosis of RCC is often delayed leading to progression and metastatic spread of the disease. Thus, validated markers for the early detection of the disease as well as selection of patients undergoing specific therapy is urgently needed. Using treatment with the monoclonal antibody (mAb) G250 as a model, proteome‐based strategies were implemented for the identification of markers which may allow the discrimination between responders and nonresponders prior to application of G250‐mediated immunotherapy. Flow cytometry revealed G250 surface expression in approximately 40% of RCC cell lines, but not in the normal kidney epithelium cell lines. G250 expression levels significantly varied thereby distinguishing between low, medium and high G250 expressing cell lines. Comparisons of two‐dimensional gel electrophoresis expression profiles of untreated RCC cell lines versus RCC cell lines treated with a mAb directed against G250 and the characterization of differentially expressed proteins by mass spectrometry and/or Edman sequencing led to the identification of proteins such as chaperones, antigen processing components, transporters, metabolic enzymes, cytoskeletal proteins and unknown proteins. Moreover, some of these differentially expressed proteins matched with immunoreactive proteins previously identified by proteome analysis combined with immunoblotting using sera from healthy donors and RCC patients, a technique called PROTEOMEX. Immunohistochemical analysis of a panel of surgically removed RCC lesions and corresponding normal kidney epithelium confirmed the heterogeneous expression pattern found by proteome‐based technologies. In conclusion, conventional proteome analysis as well as PROTEOMEX could be successfully employed for the identification of markers which may allow the selection of patients prior to specific immunotherapy.
From transcriptome to proteome: Differentially expressed proteins identified in synovial tissue of patients suffering from rheumatoid arthritis and osteoarthritis by an initial screen with a panel of 791 antibodies
Authors: Lorenz Peter , Ruschpler Peter , Koczan Dirk , Stiehl Peter , Thiesen Hans‐Jürgen
Published: June 2003

Global scale molecular profiling of diseased tissues is an important first step to unravel candidate target molecules that are involved in the pathogenesis of a disease. We have performed a comparative molecular characterization at the transcriptome (microarray with 12 526 gene specificities) and proteome level (multi‐Western blot PowerBlot™ with 791 antibodies) of synovial tissue from rheumatoid arthritis (RA) compared to osteoarthritis (OA) patients. From the panel of 791 antibodies, 260 (33%) detected their corresponding protein. Out of 58 unambiguous changes at the protein level only 16 coincided at the transcript level (28%). Stat1, p47phox and manganese superoxide dismutase were shown to be reproducibly overexpressed in RA versus OA synovial tissue by Western blots with a panel of 8 RA versus 8 OA samples. Cathepsin D was among the most prominent proteins scored to be underexpressed in RA by the PowerBlot™ whereas no differences of the respective transcript were observed. The lower abundance of cathepsin D protein in RA compared to OA tissue was also reproduced in other patient samples. Immunohistochemistry assigned the Stat1 protein in RA synovial tissue mainly to macrophages and T lymphocytes and the p47phox protein in particular to macrophages. In conclusion, our approach provided us with new candidate molecules for further analysis of rheumatic diseases and stressed the importance of studies at the protein level.
Proteomic changes in Escherichia coli TG1 after metabolic engineering for enhanced trichloroethene biodegradation
Authors: Pferdeort Valerie A. , Wood Thomas K. , Reardon Kenneth F.
Published: June 2003

Through metabolic engineering, new enzymatic pathways can be introduced into cells to enable or enhance production or biotransformation of chemicals. However, these changes have physiological consequences that can be important but are not well understood. Here we describe the use of two‐dimensional gel electrophoresis (2‐DE) to detect changes in the proteome of Escherichia coli cells that have been engineered to transform the pollutant trichloroethene (TCE) with the enzyme toluene o‐monooxygenase (TOM). Comparison of 2‐DE gels (isoelectric point range 4–7) for E. coli cells with and without the ability to synthesize TOM revealed 31 new proteins in TOM‐containing cells as well as nine proteins not detected in those cells but present in the plasmid control strain. Exposure of TOM‐containing cells to TCE led to the synthesis of four new proteins and the loss of only one protein. Thus, this example of metabolic engineering has a substantial and complex impact on the physiology of these cells that was clearly revealed using a proteomic approach.
Rotational isomerism in 3,4‐alkylenedioxy‐2,5‐bis[di(tert‐butyl)hydroxymethyl]thiophenes>
Authors: Lomas John S. , Cordier Christine
Published: June 2003

In 3,4‐ethylenedioxy‐2,5‐bis[di(tert‐butyl)hydroxymethyl]thiophene there are three rotational isomers, syn,syn (SS), anti,syn (AS) and anti,anti (AA) (syn, free; anti, hydrogen‐bonded), differing in the number (zero, one or two) of alcohol hydrogen atoms intramolecularly hydrogen bonded to the oxygen atoms of the bridge. When a methyl group is introduced into the bridge the AS rotamer can be distinguished from SA [where the first character indicates the orientation of the —C(t‐Bu)2OH group closer to the substituent] by means of a 1H NOESY experiment. Forms with ‘free’ OH groups are favoured by hydrogen‐bonding solvents, but the AS:SA ratio for the methyl derivative is solvent independent, slightly favouring the AS isomer. Whatever the solvent, the methyl group has no significant effect upon the equilibrium rotamer ratios. Rotation barriers for the various equilibria are of the order of 20 kcal mol−1. Copyright © 2003 John Wiley & Sons, Ltd.
Wettability of poly(styrene‐co‐acrylate) ionomers improved by oxygen‐plasma source ion implantation
Authors: Lim Hyuneui , Lee Yeonhee , Han Seunghee , Kim Youngwoo , Song Ju‐Myung , Kim Joon‐Seop
Published: June 2003

The surfaces of poly(styrene‐co‐acrylic acid) copolymers and their Na‐ and Cs‐neutralized ionomers were modified by O2‐plasma source ion implantation (PSII) treatment to improve the surface wettability. The changes in the surface wettability, composition, and structure upon the PSII treatment were examined with contact‐angle measurements and X‐ray photoelectron spectroscopy. The untreated surfaces of the acid copolymers and ionomers exhibited different surface energies; this implied clearly that the type of ion species affects the surface hydrophilicity. Also, the PSII treatment induced oxygen‐containing groups to reside on the surface and ionic groups to come out toward the surface; this made the surfaces of the ionomers more hydrophilic as compared with that of the acid copolymers. The ionomers also showed slow hydrophobic recovery. Thus, it was suggested that the reduced mobility of the polymer chain because of the presence of ionic aggregates results in restricted reorientation of oxygen‐containing groups. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 1791–1797, 2003
Fabrication and properties of poly(propylene carbonate)/calcium carbonate composites
Authors: Li X. H. , Tjong S. C. , Meng Y. Z. , Zhu Q.
Published: June 2003

Composites of poly(propylene carbonate) (PPC) reinforced with micrometric and nanometric calcium carbonate particles were prepared via melt mixing followed by compression molding. The morphology and mechanical and thermal behaviors of the composites were investigated. Static tensile tests showed that the tensile strength, stiffness, and ductility of the composites tended to increase with increasing contents of micrometric calcium carbonate particles. This improvement in the tensile properties was attributed to good interfacial adhesion between the fillers and matrix, as evidenced by scanning electron microscopy examination. However, because of the agglomeration of calcium carbonate nanoparticles during blending, those composites with nanoparticles exhibited the lowest tensile strength. Thermogravimetric measurements revealed that the incorporation of calcium carbonate into PPC resulted in a slight improvement in its thermooxidative stability. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 1806–1813, 2003
The experience of leukaemia and bone marrow transplant: Searching for meaning and agency
Authors: Xuereb Mary Carmen , Dunlop Rosemary
Published: June 2003

This qualitative study examines the experience of haematological cancer as described by ten people who have been through leukaemia or lymphoma and a bone marrow transplant. The focus is on the interaction of these participants with this challenging experience and the meaning it had for them. The descriptions of their thoughts, feelings and actions as they negotiated the period from diagnosis to treatment and survival reveal that these people brought both the present values in their life, as well as a life‐long pattern of dealing with adversity, into their confrontation of a life‐threatening illness. Issues of personal meaning and agency (the capacity to act and control valued aspects of one's life) were found to be paramount. These results are then discussed with a view to their implications for patient care. Copyright © 2003 John Wiley & Sons, Ltd.
Asthma mortality in the Danish child population: risk factors and causes of asthma death
Authors: Jørgensen Inger Merete , Jensen Vagn B. , Bülow Susanne , Dahm Thomas L. , Prahl Palle , Juel Knud
Published: June 2003

Child death due to asthma is a rare and potentially preventable event. We investigated possible risk factors for death due to asthma in children and adolescents, as a step towards preventing or minimizing asthma death in this age group, and improving asthma management and care. We reviewed all 108 cases of asthma death in 1–19‐year‐olds in Denmark, 1973–1994. Copies of death certificates, hospital records, information from general practicioners, and autopsy records were obtained. The information was assessed with particular reference to: features and duration of asthma before death; severity of asthma; time and place of death; long‐term and ongoing medical treatment; quality of medical care; circumstances of final illness; and medical treatment during the final episode of asthma. Age groups of 1–4 years, 5–14 years, and 15–19 years were analyzed separately and in aggregate. Death occurred predominantly in the 15–19‐year age group. Generally, significantly more patients died in the summer. These patients were more atopic, had fewer asthma symptoms, and did not have regular asthma consultations. Nearly all patients had early‐onset asthma. The 1–4‐year age group was characterized by severe asthma. Major risk factors (all age groups) were: gradual deterioration during the last month; length of final attack (>3 hr); and delay in seeking medical help during the final attack. None of the children died during their first attack. Nonadherence was most frequent among the 15–19‐year‐olds. All asthmatic children and young adults should regularly receive medical care and assessment, even if they suffer only a few symptoms. This study underlines the need for ongoing education of the patient's family, the patient, and doctors on long‐term management and management of acute attacks. Copies of clearly written individual plans for periods with increasing symptoms should be supplied to the patient/family and, where appropriate, to their general practicioners. The object of these measures is that the patient and parents/family learn to recognize the signs of deterioration and to act on them. Pediatr Pulmonol. 2003; 36:142–147. © 2003 Wiley‐Liss, Inc.
Childhood wheezing syndromes and healthcare data
Authors: Kozyrskyj Anita L. , Mustard Cameron A. , Becker Allan B.
Published: June 2003

There is convincing evidence that several distinct wheezing syndromes exist in childhood. The purpose of this research was to assess the potential of using healthcare utilization profiles to identify wheezing syndromes in children which are distinct from asthma. Using population‐based healthcare administrative data, a cohort of children, aged 5–15 years, with bronchitis diagnoses from time of birth to 1995, but no physician diagnoses of asthma, was followed over the period January 1996–March 1998. In this follow‐up period, 13% had subsequent healthcare utilization for asthma, 23% had continued healthcare utilization for bronchitis, and 64% had no further healthcare utilization. The likelihood of bronchitis vs. asthma outcomes was determined for a variety of asthma risk factors. In a cohort of 11,043 children with initial healthcare contact for bronchitis but not asthma, two potentially distinct entities of bronchitis emerged from our data: 1) transient bronchitis, similar to transient wheezing of early childhood, which was associated with winter‐only healthcare utilization and absence of allergy, and 2) recurrent bronchitis which differed from asthma on the basis of winter‐only healthcare utilization, prematurity at birth, absence of allergy, and low socioeconomic status. Healthcare administrative records can be used to describe the natural history of wheezing in children and to identify markers which may discriminate asthma from other syndromes. Pediatr Pulmonol. 2003; 36:131–136. © 2003 Wiley‐Liss, Inc.
Airway anomalies in children with Down syndrome: endoscopic findings
Authors: Bertrand Pablo , Navarro Hector , Caussade Solange , Holmgren Nils , Sánchez Ignacio
Published: June 2003

Down syndrome (DS) is the most common chromosomal anomaly in humans. Numerous congenital malformations associated with DS have been described. However, there are insufficient data available about airway anomalies. Our objective was to characterize the clinical presentation, frequency, and type of airway anomalies in a population of patients with DS. A retrospective evaluation of flexible bronchoscopies performed in 24 DS patients due to significant respiratory morbidity was compared to the findings in 324 non‐DS patients during the same time period. The procedure was carried out under sedation, using an Olympus BF3C20 bronchoscope. The main indications for the procedure were atelectasis of the right upper lobe (12/24) and stridor (7/24). The most common associated conditions were congenital heart disease (12/24) and reactive airways disease (12/24). The most important endoscopic findings were: laryngomalacia (12/24), tracheomalacia (8/24), tracheal bronchus (5/24), and bronchomalacia (5/24). Only six patients had a normal examination. Multiple airway anomalies (≥2) were a common finding in this series. We conclude that patients with DS and respiratory symptoms have a high incidence of airway anomalies compared to non‐DS patients. The clinician should have a high index of suspicion for airway anomalies in DS patients with respiratory symptoms. Pediatr Pulmonol. 2003; 36:137–141. © 2003 Wiley‐Liss, Inc.
Rolling tachyon in NS string field theory
Authors: Aref'eva I.Ya.
Published: June 2003

A brief review of studing rolling solutions to equations of motion for the tachyon field living on an unstable D‐brane in the level truncated string field theory is given.
Quantisation of gauged \documentclass{article}\usepackage{amssymb}\pagestyle{empty}\begin{document}$SL(2,\mathbb R)$\end{document} WZNW theories
Authors: Jorjadze G. , Weigt G.
Published: June 2003

Canonical quantisation of the free‐field zero modes q, p on a half‐line p > 0 provides for WZNW coset theories self‐adjoint vertex operators on account of hidden symmetries generated by an S‐matrix.
Adding flavor to AdS/CFT
Authors: Karch A. , Katz A.
Published: June 2003

Coupling fundamental quarks to QCD in the dual string representation corresponds to adding the open string sector. Flavors therefore should be represented by space‐time filling D‐branes in the dual 5d closed string background. This requires several interesting properties of D‐branes in AdS. D‐branes have to be able to end in thin air in order to account for massive quarks, which only live in the UV region. They must come in distinct sets, representing the chiral global symmetry, with a bifundamental field playing the role of the chiral condensate. We show that these expectations are born out in several supersymmetric examples. To analyze most of these properties it is not necessary to go beyond the probe limit in which one neglects the backreaction of the flavor D‐branes.
Black holes and black strings on cylinders
Authors: Harmark T. , Obers N.A.
Published: June 2003

We review the recently discovered ansatz that describes non‐extremal charged dilatonic branes of string/M‐theory with a transverse circle. The ansatz involves a new coordinate system that interpolates between the spherical and cylindrical case, and reduces the equations of motion to a set of equations on one unknown function of two variables. The function is independent of the charge, so that the ansatz can also be used to construct neutral black holes on cylinders and near‐extremal charged dilatonic branes with a transverse circle. The construction enables us to argue that, for sufficiently large mass, there exists a neutral solution that breaks translational invariance in the circle direction, and has larger entropy than that of the neutral black string of the same mass.
Asymmetrically gauged WZNW models
Authors: Quella T. , Schomerus V.
Published: June 2003

Many interesting exactly solvable backgrounds can be obtained by gauging WZNW models asymmetrically. These include the base of the conifold and the time dependent Nappi‐Witten background in which a 3‐dimensional universe passes through a series of big‐bang big‐crunch singularities. In this short note we review recent results on the conformal field theory description of asymmetric cosets. In particular, we present formulas for their bulk modular invariant partition functions and for a large number of D‐brane boundary states.
The tachyon does matter
Authors: Buchel A. , Walcher J.
Published: June 2003

We review the concept of S‐branes introduced by Gutperle and Strominger [1]. Using the effective spacetime description of the rolling tachyon worldsheets discussed by Sen, we analyze the possibility that the gravitational backreaction of tachyon matter is important in the time‐dependent process. We show that this is indeed the case in the example of the S0‐brane in 4‐dimensional Einstein‐Maxwell theory. This talk is based on [21].
Effective actions near singularities: the STU‐model
Authors: Zagermann M.
Published: June 2003

We derive the low energy effective action of the STU‐model in four and five dimensions near the line T = U, where SU(2) gauge symmetry enhancement occurs. By ‘integrating in’ the light W± bosons together with their superpartners, the quantum corrected effective action becomes non‐singular at T = U and manifestly SU(2) invariant. The four‐dimensional theory is found to be consistent with modular invariance and the five‐dimensional decompactification limit.
The Long-Run Performance of Initial Public Offerings,
Authors: Ritter Jay R.
Published: July 2003

The underpricing of initial public offerings (IPOs) that has been widely docu- mented appears to be a short-run phenomenon. Issuing firms during 1975-1984 substantially underperformed a sample of matching firms from the closing price on the first day of public trading to their three-year anniversaries. There is substantial variation in the underperformance year-to-year and across industries, with compan- ies that went public in high-volume years faring the worst. The patterns are consist- ent with an IPO market in which (1) investors are periodically overoptimistic about the earnings potential of young growth companies, and (2) firms take advantage of these “windows of opportunity. ” TheJournaZofFinance, Vol. XLVI, No. 1 (March 199 1)) pp. 3-27. (Reprinted with permission of The Journal of Finance.)
Bond Rating Discrepancies and the Effect on Municipal Bond Yields
Authors: Perry Larry G. , Evans Dorla A. , Liu Pu
Published: July 2003

This paper examines municipal bond rating discrepancies and their impact on interest yield premia. The results indicate that there is no systematic difference between Moody’s and S&P’s assigned ratings, regardless of whether generic or modified rating systems are employed. The results also indicate that when generic rating systems are used, there is no significant difference in yield premia between bonds with split ratings and bonds with equivalent ratings. Results are different, however, when modifiers are considered. Although superior and inferior S&P’s ratings (holding Moody’s ratings fixed) still do not affect the yield premium, superior ratings assigned by Moody’s (holding S&P’s fixed) do lower the interest yield premium significantly. Quarterly Journal of Business and Economics, Vol. 30, No. 1 (Winter 1991), pp. 110-127. (Reprinted with permission of the Quarterly Journal of Business and Economics.)
Problems in developing an instrument for the rapid assessment of personality status
Authors: Van Horn E. , Manley C. , Leddy D. , Cicchetti D. , Tyrer P.
Published: July 2003

Purpose

To assess the validity of a quick assessment instrument (10 minutes) for assessing personality status, the Rapid Personality Assessment Schedule (PAS-R).

Subjects and methods

The PAS-R was evaluated in psychotic patients recruited in one of the centres involved in a multicentre randomised controlled trial of intensive vs standard case management (the UK700 case management trial). Patients were assessed using both a full version of the PAS (PAS-I – ICD version) and the PAS-R. The weighted kappa statistic was used to gauge the (criterion-related) validity of the PAS-R using the PAS-I as the gold standard. Both measure code personality status using a four-point rating of severity in addition to recording individual categories of personality disorder.

Results

One hundred fifty-five (77%) of 201 patients recruited were assessed with both instruments. The weighted kappa statistic was 0.31, suggesting only moderate agreement between the PAS-I and PAS-R instruments under the four-point rating format, and 0.39 for the dichotomous personality disorder/no disorder separation. The sensitivity (64%) and specificity (82%) of the PAS-R in predicting PAS-I personality disorder were as satisfactory as for other screening instruments but still somewhat disappointing, and the PAS-R had an overall diagnostic accuracy of 78%.

Conclusion

The PAS-R is a quick and rough method of detecting personality abnormality but is not a substitute for a fuller assessment.
Envy manifestations and personality disorders
Authors: Habimana E. , Massé L.
Published: July 2003

Personality disorders are frequently associated with socially unacceptable behaviours that might not be always considered deviant. On the other hand, envy has been linked with various forms of maladjustment such as interpersonal conflicts, low self-esteem, depression, anxiety, aggressiveness, and even criminal behaviour such as vandalism and even murder. According to the DSM-IV, none of the personality disorders, except the narcissistic personality, is formally associated with envy. Nevertheless, this ‘deadly sin’ is so omnipresent in human relationships that it cannot be restricted only to the narcissistic personalities. Most scholars recognise that people would deny that they envy someone else since envy is socially considered as highly undesirable; verbal reports are expected to be biased. To circumvent this difficulty, a projective questionnaire is proposed. We constructed two questionnaires: a direct version (DV) and an indirect version (IV). The sample consisted of 786 students from high school and university. Results suggest that the indirect version provides a more accurate assessment of envy.
Genetic structure and differentiation in cultivated grape, Vitis vinifera L.
Authors: ARADHYA MALLIKARJUNA K. , DANGL GERALD S. , PRINS BERNARD H. , BOURSIQUOT JEAN-MICHEL , WALKER M. ANDREW , MEREDITH CAROLE P. , SIMON CHARLES J.
Published: June 2003

222 cultivated (Vitis vinifera) and 22 wild (V. vinifera ssp. sylvestris) grape accessions were analysed for genetic diversity and differentiation at eight microsatellite loci. A total of 94 alleles were detected, with extensive polymorphism among the accessions. Multivariate relationships among accessions revealed 16 genetic groups structured into three clusters, supporting the classical eco-geographic grouping of grape cultivars: occidentalis, pontica and orientalis. French cultivars appeared to be distinct and showed close affinity to the wild progenitor, ssp. sylvestris from south-western France (Pyrenees) and Tunisia, probably reflecting the origin and domestication history of many of the old wine cultivars from France. There was appreciable level of differentiation between table and wine grape cultivars, and the Muscat types were somewhat distinct within the wine grapes. Contingency χ2 analysis indicated significant heterogeneity in allele frequencies among groups at all loci. The observed heterozygosities for different groups ranged from 0·625 to 0·9 with an overall average of 0·771. Genetic relationships among groups suggested hierarchical differentiation within cultivated grape. The gene diversity analysis indicated narrow divergence among groups and that most variation was found within groups (∼85%). Partitioning of diversity suggested that the remaining variation is somewhat structured hierarchically at different levels of differentiation. The overall organization of genetic diversity suggests that the germplasm of cultivated grape represents a single complex gene pool and that its structure is determined by strong artificial selection and a vegetative mode of reproduction.
Non-parametric interval mapping in half-sib designs: use of midranks to account for ties
Authors: TILQUIN P. , VAN KEILEGOM I. , COPPIETERS W. , LE BOULENGÉ E. , BARET P. V.
Published: June 2003

In QTL analysis of non-normally distributed phenotypes, non-parametric approaches have been proposed as an alternative to the use of parametric tests on mathematically transformed data. The non-parametric interval mapping test uses random ranking to deal with ties. Another approach is to assign to each tied individual the average of the tied ranks (midranks). This approach is implemented and compared to the random ranking approach in terms of statistical power and accuracy of the QTL position. Non-normal phenotypes such as bacteria counts showing high numbers of zeros are simulated (0–80% zeros). We show that, for low proportions of zeros, the power estimates are similar but, for high proportions of zeros, the midrank approach is superior to the random ranking approach. For example, with a QTL accounting for 8% of the total phenotypic variance, a gain from 8% to 11% of power can be obtained. Furthermore, the accuracy of the estimated QTL location is increased when using midranks. Therefore, if non-parametric interval mapping is chosen, the midrank approach should be preferred. This test might be especially relevant for the analysis of disease resistance phenotypes such as those observed when mapping QTLs for resistance to infectious diseases.
Administration and innovation at Turin's Teatro Regio: producing Sofonisba (1764) and Oreste (1766)
Authors: BUTLER MARGARET
Published: June 2003

Opera seria underwent more change in the latter part of the eighteenth century than is commonly recognized, but the nature of the change often had as much to do with practical considerations as with aesthetic ideology. This essay focuses on Turin's Teatro Regio, which in the 1760s imported two particularly innovative operas, Sofonisba and Oreste, and retained some ‘‘progressive” features while discarding others. This essay demonstrates the importance of extra-musical factors in decisions regarding production.
Mesmerizing adultery: Così fan tutte and the Kornman scandal
Authors: POLZONETTI PIERPAOLO
Published: June 2003

A notorious adultery scandal involving Guillaume Kornman (a co-founder and sponsor of the French mesmeric society) and Beaumarchais, who defended Kornman’s unfaithful wife, should be considered one of the main sources of inspiration for Così fan tutte. A pamphlet war between the two broke out in 1787, when Salieri was living with Beaumarchais in Paris. Significantly, the earliest sources of the opera – Salieri's first unfinished setting of La scola degli amanti, Da Ponte's original libretto, and Mozart's autograph – all spell the name of Guglielmo as ‘Guilelmo.’ A study of this real-life Parisian drama helps to clarify several dramatic and musical elements of the opera, including the use of mesmeric references, which is more pervasive than previously recognized. In this new light, the opera appears to offer a political response to the radical ideas on the regulation of sexual and social matters disseminated by Kornman's mesmeric circle.
Neapolitan elements and comedy in nineteenth-century opera buffe
Authors: WERR SEBASTIAN
Published: June 2003

This essay examines the attributes of some typical opere buffe by Vincenzo Fioravanti, Nicola De Giosa, and Errico Petrella that may count as particularly Neapolitan. Contextualizing these ‘Neapolitan’ elements – especially the ‘Neapolitan characters’ like Pulcinella, and the use of local dialect and spoken dialogue – demonstrates their function in the comedy of these works, which rests on the multifarious, complex and yet direct connections between theatrical events and the real world surrounding them.
The trial, the condemnation, the cover-up: behind the scenes of Brecht/Dessau's Lucullus opera(s)
Authors: CALICO JOY
Published: June 2003

According to conventional wisdom, East German censorship of The Trial Of Lucullus (1951) required that composer Paul Dessau and librettist Bertolt Brecht completely overhaul the opera before it could be re-premièred later that year as The Condemnation Of Lucullus. However, archival sources prove that the two versions are virtually identical, suggesting that the attendant controversy was adroitly managed by East German officials to appease both internal/Soviet and the external/Western audiences. Analysis of several versions of scene 8 demonstrates that Dessau revised far more before the first première than after, and examines his use of musical style to symbolize sociopolitical status.
Bioprospecting and biodiversity contracts
Authors: Mulholland Denise M. , Wilman Elizabeth A.
Published: June 2003

A dynamic economic model for a biodiversity prospecting contract, between a host country and a pharmaceutical company, is developed and used to explain the structure of existing contracts. The host country's stocks of biodiversity and genetic information are crucial inputs to the production of high-quality samples. Even with compete property rights contracts will be second best; it is not possible to perfectly monitor host-country inputs to the drug discovery process. Contracts vary due to the different degrees of observability of host-country inputs, and incomplete or ineffective property rights.
Influence of Inflammatory Cytokines on Arteriogenesis
Authors: BUSCHMANN IVO , HEIL MATTHIAS , JOST MARCO , SCHAPER WOLFGANG
Published: July 2003

Blood vessel growth after birth is limited to two major processes. Angiogenesis is the growth of new capillaries by sprouting or intussusception. The major stimulus for angiogenesis is ischemia. In contrast, arteriogenesis describes the remodeling and growth of collateral arteries from a preexisting arteriolar network. Arteriogenesis is induced after the occlusion of a major artery which induces hemodynamic and mechanical effects on the collateral vessel wall which occur with increasing blood flow velocity due to the low pressure at the reentrant site of the collateral vessel. A variety of different cytokines that act by stimulating endothelial and smooth muscle cell proliferation and migration or recruitment and activation of monocytes have been identified to stimulate angiogenesis and/or arteriogenesis (i.e., MCP‐1, FGF‐2, TGF‐ß, VEGF, and GM‐CSF). Several clinical trials have been published in that field to suggest the feasibility and safety of treatment with such cytokines or their genes. However, the results indicate that further studies are needed before proangiogenic and proarteriogenic therapies are ready for clinical application.
Antisense-mediated loss of calcium homoeostasis endoplasmic reticulum protein (CHERP; ERPROT213-21) impairs Ca2+ mobilization, nuclear factor of activated T-cells (NFAT) activation and cell proliferation in Jurkat T-lymphocytes
Authors: O'ROURKE Flavia A. , LaPLANTE Janice M. , FEINSTEIN Maurice B.
Published: June 2003

We recently discovered a novel gene on chromosome 19p13.1 and its product, an integral endoplasmic reticulum (ER) membrane protein, termed CHERP (calcium homoeostasis endoplasmic reticulum protein). A monoclonal antibody against its C-terminal domain inhibits Ins(1,4,5)P3-induced Ca2+ release from ER membrane vesicles of many cell types, and an antisense-mediated knockdown of CHERP in human erythroleukemia (HEL) cells greatly impaired Ca2+ mobilization by thrombin. In the present paper, we explore further CHERP's function in Jurkat T-lymphocytes. Confocal laser immunofluorescence microscopy showed that CHERP was co-localized with the Ins(1,4,5)P3 receptor throughout the cytoplasmic and perinuclear region, as previously found in HEL cells. Transfection of Jurkat cells with a lacI-regulated mammalian expression vector containing CHERP antisense cDNA caused a knockdown of CHERP and impaired the rise of cytoplasmic Ca2+ (measured by fura-2 acetoxymethyl ester fluorescence) caused by phytohaemagglutinin (PHA) and thrombin. A 50% fall of CHERP decreased the PHA-induced rise of the cytoplasmic free Ca2+ concentration ([Ca2+]i), but Ca2+ influx was unaffected. Greater depletion of CHERP (>70%) did not affect the concentration of Ins(1,4,5)P3 receptors, but diminished the rise of [Ca2+]i in response to PHA to ≤30% of that in control cells, decreased Ca2+ influx and slowed the initial rate of [Ca2+]i rise caused by thapsigargin, an inhibitor of the sarcoplasmic/endoplasmic-reticulum Ca2+-ATPase, suggesting there was also some deficit in ER Ca2+ stores. In CHERP-depleted cells the Ca2+-dependent activation and translocation of the key transcription factor NFAT (nuclear factor of activated T-cells) from cytoplasm to nucleus was suppressed. Furthermore, cell proliferation was greatly slowed (as in HEL cells) along with a 60% decrease in cyclin D1, a key regulator of progression through the G1 phase of the cell cycle. These findings provide further evidence that CHERP is an important component of the ER Ca2+-mobilizing system in cells, and its loss impairs Ca2+-dependent biochemical pathways and progression through the cell cycle.
Localization of a highly active pool of type II phosphatidylinositol 4-kinase in a p97/valosin-containing-protein-rich fraction of the endoplasmic reticulum
Authors: WAUGH Mark G. , MINOGUE Shane , ANDERSON J. Simon , BALINGER Adam , BLUMENKRANTZ Deena , CALNAN Denis P. , CRAMER Rainer , HSUAN J. Justin
Published: June 2003

Different phosphoinositides are synthesized in cell membranes in order to perform a variety of functions. One of the most abundant of these lipids is phosphatidylinositol (PI) 4-phosphate (PI4P), which is formed in human eukaryotes by type II and type III phosphatidylinositol 4-kinase (PI4K II and III) activities. PI4K II activity occurs in many different subcellular membranes, although no detailed analysis of the distribution of this activity has been reported. Using density gradient ultracentrifugation, we have previously found that in A431 cells the predominant PI4K activity arises from a type IIα enzyme that is localized to a buoyant membrane fraction of unknown origin [Waugh, Lawson, Tan and Hsuan (1998) J. Biol. Chem. 273, 17115–17121]. We show here that these buoyant membranes contain an activated form of PI4K IIα that can be separated from the bulk of the PI4K IIα protein in A431 and COS-7 cells. Proteomic analysis revealed that the buoyant membrane fraction contains numerous endoplasmic reticulum (ER)-marker proteins, although it was separated from the bulk of the ER, ER–Golgi intermediate compartment, transitional ER, Golgi and other major subcellular membranes. Furthermore, the majority of the cytoplasmic valosin-containing protein (VCP), an AAA+ATPase implicated in various ER, transitional ER, Golgi and nuclear functions, was almost completely localized to the same buoyant membrane fraction. Co-localization of VCP and PI4K activity was confirmed by co-immunoprecipitation. These results suggest the previously unsuspected existence of an ER-related domain in which the bulk of the cellular PI4P synthesis and VCP are localized.
Cytosolic glucocorticoid receptor interaction with nuclear factor-kappaB proteins in rat liver cells
Authors: WIDÉN Christina , GUSTAFSSON Jan-Åke , WIKSTRÖM Ann-Charlotte
Published: June 2003

The glucocorticoid receptor (GR) acts as an anti-inflammatory factor. To a large extent, this activity is exerted by the interference of pro-inflammatory nuclear factor κB (NF-κB) activity. In their respective inactive forms, both GR and NF-κB reside in the cytoplasm and translocate to the nucleus on relevant stimulation. Previously, p65, a component of the NF-κB complex, and GR have been shown to interact physically in vitro, and the interaction is assumed to take place in the nucleus of cells [McKay and Cidlowski (1999) Endocrine Rev. 20, 435–459]. We have studied the interaction between GR and NF-κB using in vivo-like conditions. Using immunoaffinity chromatography or immunoprecipitation, combined with Western blotting, we observed that, with endogenous protein levels in cytosolic extracts of rat liver and of H4-II-E-C3 hepatoma cells and in contrast with the current belief, p65, p50 and inhibitory κBα complex interact with GR, even in the absence of glucocorticoid or an inflammatory signal. The interaction between non-liganded/non-activated GR and p65/p50 has also been verified by both p65 and p50 co-immunoprecipitations. Intracellular localization studies, using Western blotting, revealed that glucocorticoids can decrease tumour necrosis factor α (TNFα)-induced nuclear entry of p65, whereas glucocorticoid-induced GR translocation was much less affected by TNFα. We were also able to demonstrate a nuclear interaction of GR and p65 and p50 using in vivo-like protein concentrations. Furthermore, nuclear GR interaction with heat-shock protein 90 was enhanced distinctly by TNFα treatment. In conclusion, our studies suggest a strong interconnectivity between the NF-κB and GR-signalling pathways where also, somewhat unexpectedly, a physical interaction in the cytosol constitutes an integral part of GR–NF-κB cross-talk.
Characterization of the human, mouse and rat PGC1beta (peroxisome-proliferator-activated receptor-gamma co-activator 1beta) gene in vitro and in vivo
Authors: MEIRHAEGHE Aline , CROWLEY Vivion , LENAGHAN Carol , LELLIOTT Christopher , GREEN Kath , STEWART Abigail , HART Kevin , SCHINNER Sven , SETHI Jaswinder K. , YEO Giles , BRAND Martin D. , CORTRIGHT Ron N. , O'RAHILLY Stephen , MONTAGUE Carl , VIDAL-PUIG Antonio J.
Published: June 2003

PGC1α is a co-activator involved in adaptive thermogenesis, fatty-acid oxidation and gluconeogenesis. We describe the identification of several isoforms of a new human PGC1α homologue, cloned independently and named PGC1β. The human PGC1β gene is localized to chromosome 5, has 13 exons and spans more than 78 kb. Two different 5′ and 3′ ends due to differential splicing were identified by rapid amplification of cDNA ends PCR and screening of human cDNA libraries. We show that PGC1β variants in humans, mice and rats are expressed predominantly in heart, brown adipose tissue, brain and skeletal muscle. PGC1β expression, unlike PGC1α, is not up-regulated in brown adipose tissue in response to cold or obesity. Fasting experiments showed that PGC1α, but not PGC1β, is induced in liver and this suggests that only PGC1α is involved in the hepatic gluconeogenesis. No changes in PGC1β gene expression were observed associated with exercise. Human PGC1β-1a and −2a isoforms localized to the cell nucleus and, specifically, the isoform PGC1β-1a co-activated peroxisome-proliferator-activated receptor-γ, -α and the thyroid hormone receptor β1. Finally, we show that ectopic expression PGC1β leads to increased mitochondrial number and basal oxygen consumption. These results suggest that PGC1β may play a role in constitutive adrenergic-independent mitochondrial biogenesis.
Deep-apical tubules: dynamic lipid-raft microdomains in the brush-border region of enterocytes
Authors: HANSEN Gert H. , PEDERSEN Jens , NIELS-CHRISTIANSEN Lise-Lotte , IMMERDAL Lissi , DANIELSEN E. Michael
Published: June 2003

The brush border of small intestinal enterocytes is highly enriched in cholesterol- and glycosphingolipid-containing membrane microdomains, commonly termed as lipid ‘rafts’. Functionally, transcytosis of IgA and exocytosis of newly made brush-border proteins in enterocytes occur through apical lipid raft-containing compartments, but little is otherwise known about these raft microdomains. We therefore studied in closer detail apical lipid-raft compartments in enterocytes by immunogold electron microscopy and biochemical analyses. Novel membrane structures, deep-apical tubules, were visualized by the non-permeable surface marker Ruthenium Red in the brush-border region of the cells. The surface-connected tubules were labelled by antibodies to caveolin-1 and the glycolipid asialo GM1, and they were sensitive to cholesterol depletion by methyl-β-cyclodextrin, indicating the presence of raft microdomains. Deep-apical tubules were positioned close to the actin rootlets of adjacent microvilli in the terminal web region, which had a diameter of 50–100 nm, and penetrated up to 1 μm into the cytoplasm. Markers for transcytosis, IgA and the polymeric immunoglobulin receptor, as well as the resident brush-border enzyme aminopeptidase N, were present in these deep-apical tubules. We propose that deep-apical tubules are a specialized lipid-raft microdomain in the brush-border region functioning as a hub in membrane trafficking at the brush border. In addition, the sensitivity to cholesterol depletion suggests that deep-apical tubules function as a cell-surface membrane reservoir for cholesterol and for rapid adaptive changes in the size of microvilli at the brush border.
Molecular characterization of recombinant T1, a non-allergenic periwinkle (Catharanthus roseus) protein, with sequence similarity to the Bet v 1 plant allergen family
Authors: LAFFER Sylvia , HAMDI Said , LUPINEK Christian , SPERR Wolfgang R. , VALENT Peter , VERDINO Petra , KELLER Walter , GROTE Monika , HOFFMANN-SOMMERGRUBER Karin , SCHEINER Otto , KRAFT Dietrich , RIDEAU Marc , VALENTA Rudolf
Published: June 2003

More than 25% of the population suffer from Type I allergy, an IgE-mediated hypersensitivity disease. Allergens with homology to the major birch (Betula verrucosa) pollen allergen, Bet v 1, belong to the most potent elicitors of IgE-mediated allergies. T1, a cytokinin-inducible cytoplasmic periwinkle (Catharanthus roseus) protein, with significant sequence similarity to members of the Bet v 1 plant allergen family, was expressed in Escherichia coli. Recombinant T1 (rT1) did not react with IgE antibodies from allergic patients, and failed to induce basophil histamine release and immediate-type skin reactions in Bet v 1-allergic patients. Antibodies raised against purified rT1 could be used for in situ localization of natural T1 by immunogold electron microscopy, but did not cross-react with most of the Bet v 1-related allergens. CD analysis showed significant differences regarding secondary structure and thermal denaturation behaviour between rT1 and recombinant Bet v 1, suggesting that these structural differences are responsible for the different allergenicity of the proteins. T1 represents a non-allergenic member of the Bet v 1 family that may be used to study structural requirements of allergenicity and to engineer hypo-allergenic plants by replacing Bet v 1-related allergens for primary prevention of allergy.
Amino acid transporters: roles in amino acid sensing and signalling in animal cells
Authors: HYDE Russell , TAYLOR Peter M. , HUNDAL Harinder S.
Published: June 2003

Amino acid availability regulates cellular physiology by modulating gene expression and signal transduction pathways. However, although the signalling intermediates between nutrient availability and altered gene expression have become increasingly well documented, how eukaryotic cells sense the presence of either a nutritionally rich or deprived medium is still uncertain. From recent studies it appears that the intracellular amino acid pool size is particularly important in regulating translational effectors, thus, regulated transport of amino acids across the plasma membrane represents a means by which the cellular response to amino acids could be controlled. Furthermore, evidence from studies with transportable amino acid analogues has demonstrated that flux through amino acid transporters may act as an initiator of nutritional signalling. This evidence, coupled with the substrate selectivity and sensitivity to nutrient availability classically associated with amino acid transporters, plus the recent discovery of transporter-associated signalling proteins, demonstrates a potential role for nutrient transporters as initiators of cellular nutrient signalling. Here, we review the evidence supporting the idea that distinct amino acid “receptors” function to detect and transmit certain nutrient stimuli in higher eukaryotes. In particular, we focus on the role that amino acid transporters may play in the sensing of amino acid levels, both directly as initiators of nutrient signalling and indirectly as regulators of external amino acid access to intracellular receptor/signalling mechanisms.