bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved quality of life after lung transplantation in individuals with cystic fibrosis
Authors: Vermeulen Karin M. , van der Bij Wim , Erasmus Michiel E. , Duiverman Eric J. , Koëter Gerard H. , TenVergert Elisabeth M.
Published: April 2004

The aim of the present study was to assess the effect of lung transplantation (LgTX) on health‐related quality of life (HRQL) in a group of patients with cystic fibrosis (CF), compared to patients with other diagnoses (non‐CF). HRQL was assessed before transplantation in a group of 32 CF patients and 183 non‐CF patients. After LgTX, we conducted a prospective longitudinal study among 10 CF patients and 35 non‐CF patients who survived at least 31 months after LgTX. Measures were the Nottingham Health Profile (NHP), the State‐Trait Anxiety Inventory (STAI), the Self‐Rating Depression Scale (ZUNG), the Index of Well‐Being (IWB), and the Karnofsky Performance Index. Patients in the CF group were younger, spent more days on the waiting list, and were more likely to be working or going to school than patients with other indications. Before transplantation, CF patients and non‐CF patients experienced restrictions on almost all HRQL measures, compared to the general population. On the NHP dimensions of mobility and energy, CF patients had significantly better scores than non‐CF patients. Between 1–4 months after transplantation, scores on the NHP, ZUNG, and Karnofsky performance indices improved, and STAI and IWB scores even occurred within the reference value in both groups. Significantly better scores in the CF group compared to the non‐CF group were found on the NHP dimension of mobility 4 months after transplantation, and on the dimension of sleep 7 and 13 months after transplantation. Scores remained more or less stable over time in both groups. It may be concluded that patients in both groups experience major restrictions in HRQL before transplantation. However, pretransplant non‐CF patients experience more restrictions than CF patients. After LgTX, both groups of patients showed substantial improvement in HRQL, and this improvement was maintained until 31 months after LgTX. Pediatr Pulmonol. 2004; 37:419–426. © 2004 Wiely‐Liss, Inc.
Parent‐reported asthma in Puerto Rican children
Authors: Nazario Sylvette , Casal Jesus R. , Torres‐Palacios Alfonso , Rodriguez William , Delamater Alan M. , Applegate E. Brooks , Piedimonte Giovanni , Wanner Adam
Published: April 2004

We conducted a survey to determine parent‐reported asthma prevalence, morbidity, and healthcare utilization among 3,527 children attending public schools (n = 2,849) and private schools (n = 678) in San Juan, Puerto Rico. Schools were randomly selected from each of 12 geographic regions of the San Juan metropolitan area. Parents of children age 4–7 years old completed a 12‐item questionnaire on asthma diagnosis, respiratory symptoms and morbidity, and healthcare utilization. Parents of children in public schools and private schools reported similar rates of a physician having previously diagnosed asthma in their children (43.2% vs. 39.4%); however, significantly more children in public schools were reported to still have asthma at the time of the survey (32.6% vs. 23.7%). Children attending public schools vs. private schools were reported to have missed significantly more school and to have had more hospitalizations and emergency department visits. Among children reported to still have asthma, significantly more children visited an emergency department, were hospitalized, and missed more school days due to respiratory symptoms in the past year. The high prevalence of parent‐reported asthma, respiratory symptoms, and healthcare utilization among Puerto Rican children in San Juan calls for further studies using objective methods for ascertaining asthma and asthma‐related morbidity. Differences in healthcare utilization between children attending public vs. private schools suggest that socioeconomic factors play a role in asthma management in Puerto Rico. Pediatr Pulmonol. 2004; 37:453–460. © 2004 Wiely‐Liss, Inc.
Pulmonary exacerbations in cystic fibrosis
Authors: Rabin Harvey R. , Butler Steven M. , Wohl Mary Ellen B. , Geller David E. , Colin Andrew A. , Schidlow Daniel V. , Johnson Charles A. , Konstan Michael W. , Regelmann Warren E.
Published: April 2004

The clinical characteristics most relevant to the decision to treat for a pulmonary exacerbation with antibiotics in cystic fibrosis patients were determined. Variables including age, increased cough frequency and sputum production, new crackles and wheezing, asthma, symptomatic sinusitis, hemoptysis, decreased lung function, weight loss, and new acquisition of Pseudomonas aeruginosa were collected in a large prospective multicenter database (Epidemiologic Study of Cystic Fibrosis). During a 12‐month baseline period, data from 11,692 patients were compared with data collected during the subsequent 6‐month study period. Because pulmonary function assessments were unavailable for patients <6 years of age, separate analyses were done for those <6 and ≥6 years of age. The outcome of interest was any antibiotic treatment in the 6‐month study period reported as indicated for an exacerbation. Characteristics with the most discriminatory power were determined using stepwise multiple logistic regression. For patients <6 years of age, the strongest independent associations with treatment for a pulmonary exacerbation were new crackles, increased cough frequency, decline in weight, and increased sputum production. For those patients ≥6 years of age, the strongest independent associations were a relative decrease in percent predicted forced expired volume in 1 sec, increased cough frequency, new crackles, and hemoptysis. The presence of three or more of these key characteristics was strongly associated with the occurrence of a treated exacerbation. The reproducibility of the model over time was confirmed by application to a subsequent set of data. This model has potential for use as an outcome measure in clinical trials, and to assist in treatment decisions for individual patients. Pediatr Pulmonol. 2004; 37:400–406. © 2004 Wiely‐Liss, Inc.
Mortality after pediatric lung transplantation: Autopsies vs. clinical impression
Authors: Kaditis Athanasios G. , Phadke Shruti , Dickman Paul , Webber Steven , Kurland Geoffrey , Michaels Marian G.
Published: April 2004

Appreciable mortality accompanies pediatric lung and heart‐lung transplantation. The objective of this investigation was to compare the clinical impression of causes of death with autopsy findings in all pediatric lung or heart lung transplant recipients who had an autopsy performed between 1985–2002 at the Children's Hospital of Pittsburgh. Medical records and autopsy findings were reviewed. Thirty recipients with autopsies had 33 transplant procedures: heart‐lung (16), double lung (14), repeat lung (2), and repeat heart‐lung (1). Perioperative deaths occurred in 8 children, most often precipitated by graft dysfunction. Early deaths (2 weeks–1 year) occurred in 12 children resulting from infection. Late deaths (greater than 1 year) occurred in 10 children. Bronchiolitis obliterans complicated by infection was the major cause of death in these recipients. An autopsy confirmed the clinical impression of cause of death in 29/30 and added significant supplemental information in 16 cases. Unsuspected factors contributing to death included donor lung abnormalities, concurrent infection, and cardiovascular disease. Postmortem examination remains a critical component to augment the understanding of causes of death following pediatric thoracic transplantation. © 2004 Wiley‐Liss, Inc.
Dynamics and energetics of water permeation through the aquaporin channel
Authors: Vidossich Pietro , Cascella Michele , Carloni Paolo
Published: April 2004

Structural properties of water inside bovine aquaporin‐1 are investigated by molecular simulation. The calculations, which are based on the recently determined X‐ray structure at 2.2 Å resolution (Sui et al., Nature 2001;414:872–878), are carried out on one monomeric subunit immersed in a water‐n‐octane‐water bilayer. Molecular dynamics (MD) simulations suggest that His182, a fully conserved residue in the channel pore, is protonated in the δ position. Furthermore, they reveal a highly ordered water structure in the channel, induced by the electrostatic properties of the protein. Multiple‐steering MD simulations are used to calculate the free‐energy of water diffusion. To the best of our knowledge, this represents the first free‐energy calculation based on the new, high‐resolution structure of the pore. The calculated barrier is 2.5 kcal/mol, and it is associated to water permeation through the Asn‐Pro‐Ala (NPA) region of the pore, where water molecules are only hydrogen‐bonded with themselves. These findings are fully consistent with those based on the previous MD studies on the human protein (de Groot and Grubmüller, Science 2001;294:2353–2357). Proteins 2004. © 2004 Wiley‐Liss, Inc.
Crystal structure of human L‐xylulose reductase holoenzyme: Probing the role of Asn107 with site‐directed mutagenesis
Authors: El‐Kabbani Ossama , Ishikura Shuhei , Darmanin Connie , Carbone Vincenzo , Chung Roland P.‐T. , Usami Noriyuki , Hara Akira
Published: April 2004

L‐Xylulose reductase (XR), an enzyme in the uronate cycle of glucose metabolism, belongs to the short‐chain dehydrogenase/reductase (SDR) superfamily. Among the SDR enzymes, XR shows the highest sequence identity (67%) with mouse lung carbonyl reductase (MLCR), but the two enzymes show different substrate specificities. The crystal structure of human XR in complex with reduced nicotinamide adenine dinucleotide phosphate (NADPH) was determined at 1.96 Å resolution by using the molecular replacement method and the structure of MLCR as the search model. Features unique to human XR include electrostatic interactions between the N‐terminal residues of subunits related by the P‐axis, termed according to SDR convention, and an interaction between the hydroxy group of Ser185 and the pyrophosphate of NADPH. Furthermore, identification of the residues lining the active site of XR (Cys138, Val143, His146, Trp191, and Met200) together with a model structure of XR in complex with L‐xylulose, revealed structural differences with other members of the SDR family, which may account for the distinct substrate specificity of XR. The residues comprising a recently proposed catalytic tetrad in the SDR enzymes are conserved in human XR (Asn107, Ser136, Tyr149, and Lys153). To examine the role of Asn107 in the catalytic mechanism of human XR, mutant forms (N107D and N107L) were prepared. The two mutations increased Km for the substrate (>26‐fold) and Kd for NADPH (95‐fold), but only the N107L mutation significantly decreased kcat value. These results suggest that Asn107 plays a critical role in coenzyme binding rather than in the catalytic mechanism. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Atomic insight into the CD4 binding‐induced conformational changes in HIV‐1 gp120
Authors: Hsu Shang‐Te D. , Bonvin Alexandre M.J.J.
Published: April 2004

The entry of HIV‐1 into a target cell requires gp120 and receptor CD4 as well as coreceptor CCR5/CXCR4 recognition events associated with conformational changes of the involved proteins. The binding of CD4 to gp120 is the initiation step of the whole process involving structural rearrangements that are crucial for subsequent pathways. Despite the wealth of knowledge about the gp120/CD4 interactions, details of the conformational changes occurring at this stage remain elusive. We have performed molecular dynamics simulations in explicit solvent based on the gp120/CD4/CD4i crystal structure in conjunction with modeled V3 and V4 loops to gain insight into the dynamics of the binding process. Three differentiated interaction modes between CD4 and gp120 were found, which involve electrostatics, hydrogen bond and van der Waals networks. A “binding funnel” model is proposed based on the dynamical nature of the binding interface together with a CD4‐attraction gradient centered in gp120 at the CD4‐Phe43‐binding cavity. Distinct dynamical behaviors of free and CD4‐bound gp120 were monitored, which likely represent the ground and pre‐fusogenic states, respectively. The transition between these states revealed concerted motions in gp120 leading to: i) loop contractions around the CD4‐Phe43‐insertion cavity; ii) stabilization of the four‐stranded “bridging sheet” structure; and iii) translocation and clustering of the V3 loop and the bridging sheet leading to the formation of the coreceptor binding site. Our results provide new insight into the dynamic of the underlying molecular recognition mechanism that complements the biochemical and structural studies. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Topological thermal instability and length of proteins
Authors: Burioni Raffaella , Cassi Davide , Cecconi Fabio , Vulpiani Angelo
Published: April 2004

We present an analysis of the effects of global topology on the structural stability of folded proteins in thermal equilibrium with a heat bath. For a large class of single domain proteins, we computed the harmonic spectrum within the Gaussian Network Model (GNM) and determined their spectral dimension, a parameter describing the low frequency behavior of the density of modes. We found a surprisingly strong correlation between the spectral dimension and the number of amino acids in the protein. Considering that larger spectral dimension values relate to more topologically compact folded states, our results indicate that, for a given temperature and length of protein, the folded structure corresponds to a less compact folding, one compatible with thermodynamic stability. Proteins 2004. © 2004 Wiley‐Liss, Inc.
A new perspective on analysis of helix–helix packing preferences in globular proteins
Authors: Trovato Antonio , Seno Flavio
Published: April 2004

For many years, statistical analysis of protein databanks has led to the belief that the steric compatibility of helix interfaces may be the source of observed preferences for particular angles between neighboring helices. Several elegant models describing how side chains on helices can interdigitate without steric clashes were able to account quite reasonably for the observed distributions. However, it was later recognized that the ‘bare’ measured angle distribution should be corrected to avoid statistical bias.1, 2 Disappointingly, the rescaled distributions dramatically lost their similarity with theoretical predictions, casting doubts on the validity of the geometrical assumptions and models. In this article, we elucidate a few points concerning the proper choice of a random reference distribution. In particular we demonstrate the need for corrections induced by unavoidable uncertainties in determining whether two helices are in face‐to‐face contact or not and their relative orientations. By using this new rescaling, we show that ‘true’ packing angle preferences are well described by regular packing models, thus proving that preferential angles between contacting helices do exist. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Bicyclic Organo‐Peptides as Selective Carbohydrate Receptors: Design, Solid‐phase Synthesis, and on‐bead Binding Capability
Authors: Benito Juan M. , Meldal Morten
Published: April 2004

Selective recognition of monosaccharides in polar media by conformationally restricted bicyclic peptides containing an aromatic surface to facilitate the initial interaction has been examined. Molecular modeling assisted design of these peptidic receptors has been employed to optimize guest fitting in the peptide cavity. Different solid‐phase synthetic approaches to the target structures are discussed in order to develop a flexible methodology suitable for a combinatorial approach. A series of putative receptors, differing in the aromatic spacer as well as the peptide ring size, has been synthesized and characterized by HPLC and HR‐MS. They have been subjected to FRET‐based screening for binding to mono and disaccharides. This indicates that binding properties are strongly dependent on the size and rigidity of the receptors, detecting β‐glucoside selectivity in the case of a naphthyl‐bridged cyclic dodecapeptide. In addition, an ES‐MS/MS‐based method that allows structural elucidation of single bead samples with no need of encoding techniques has been devised, which will be useful for structure elucidation in libraries of cyclic peptides.
Synthesis of 3‐Boc‐(1,3)‐oxazinane‐Protected Amino Aldehydes from Amino Acids and Their Conversion into Urea Precursors. Novel Building Blocks for Combinatorial Synthesis
Authors: Diness F. , Beyer J. , Meldal Morten
Published: April 2004

Starting from the large pool of chiral amino acids a route to protected amino aldehyde building blocks for combinatorial chemistry has been developed. Eight α‐amino aldehydes have been synthesized from Cbz‐ or Fmoc‐protected α‐amino acids through partial reduction of Weinreb amides or partial oxidation with Dess‐Martin periodinane of amino alcohols. The α‐amino aldehydes have been protected as their acid labile 3‐Boc‐(1,3)‐oxazinanes using aminopropanol and sodium sulfate followed by treatment with Boc2O. Noteworthy, both reduction and protection proceed with minimal epimerization. 3‐Boc‐(1,3)‐oxazinane (Box) protected 2‐amino‐benzaldehyd have also been synthesized.
Molecular Connectivity: Polarity Correction to Improve Correlation with Hydrophobicity
Authors: Dearden John C. , Wong Elaine H. Y. , Walker John D.
Published: April 2004

Contrary to belief in some quarters, molecular connectivites correlate only very poorly with hydrophobicity. We have devised a simple polarity correction to the calculation of first‐order molecular connectivity (1χ), which involves subtracting, instead of adding, the bond contributions (δ values) for bonds between atoms i and j where j is a heteroatom other than halogen, to give a 1χp value. For a set of 23 diverse substituents, the correlation between 1χ and π (the hydrophobic substituent constant) yielded r2=0.123, whilst that between 1χp and π yielded r2=0.771. When the method was applied to the correlation of the protein‐binding constants for a set of 42 diverse compounds with 1χ, r2 improved from 0.078 to 0.443.
CODES/Neural Network Model: a Useful Tool for in Silico Prediction of Oral Absorption and Blood‐Brain Barrier Permeability of Structurally Diverse Drugs
Authors: Dorronsoro Isabel , Chana Antonio , Abasolo Ma Inés , Castro Ana , Gil Carmen , Stud Manfred , Martinez Ana
Published: April 2004

Two different neural network models able to predict both oral absorption (OA) and blood‐brain barrier (BBB) permeability of structurally diverse drugs in use clinically are presented here. Using the descriptors generated by CODES, a program which codifies molecules from a topological point of view, we avoid the uncertain choice of molecular conformation and physicochemical parameters. In this work, a method called Reduction of Dimensions, designed for compressing data, is applied for the first time in order to minimize the bias factor added to a QSAR study when the selection of descriptors are performed.
QSTR with Extended Topochemical Atom Indices. 3. Toxicity of Nitrobenzenes to Tetrahymena pyriformis
Authors: Roy Kunal , Ghosh Gopinath
Published: April 2004

The experimental determination of toxicological properties of commercial chemicals being costly and time consuming process, there is a need to develop mathematical predictive tool to theoretically quantify such properties. In this background, we have modeled toxicity of nitrobenzene derivatives to Tetrahymena pyriformis using extended topochemical atom (ETA) indices recently introduced by us (Roy and Ghosh, 2003). We have also modeled the toxicity data using other topological descriptors (Balaban J, kappa shape indices, connectivity indices, Wiener index) and two physicochemical variables (AlogP98, MolRef) and compared the ETA models with non‐ETA ones. Principal component factor analysis was used as the data‐preprocessing step to reduce the dimensionality of the data matrix and identify the important variables that are devoid of collinearities. Multiple linear regression analyses show that the best non‐ETA model involves 2κ and AlogP98 as predictor variables and the quality of the relation is as follows: n=42, Q2=0.70, R$ {_{{a}}^{2}}$=0.75, R2=0.76, R=0.87, F=61.0 (df 2, 39), s=0.36. On the other hand, the best ETA model has the following quality: n=42, Q2=0.88, R$ {_{{a}}^{2}}$=0.91, R2=0.92, R=0.96, F=101.4 (df 4, 37), s=0.22. The ETA relations showed positive contributions of molecular bulk (size), halogen and additional nitro substitutions in the nitrobenzene ring and negative contributions of the substituents like methyl and hydroxymethyl groups to the toxicity. An attempt to use non‐ETA descriptors along with the ETA ones slightly improves the quality in comparison to the best ETA model. Interestingly, the ETA model developed by us for the nitrobenzene toxicity is comparable to the previously reported models on the same data set (Estrada et al., 2001; Cronin et al., 1998). Thus, it appears that the ETA descriptors have significant potential in QSAR/QSPR/QSTR studies, which warrants extensive evaluation.
Screening for novel essential genes of Saccharomyces cerevisiae involved in protein secretion
Authors: Davydenko Svetlana G. , Juselius Jukka K. , Munder Thomas , Bogengruber Edith , Jäntti Jussi , Keränen Sirkka
Published: April 2004

We describe here a screening procedure devised for searching new genes involved in protein secretion in Saccharomyces cerevisiae. The screening procedure takes advantage of yeast strains constructed within the EUROFAN project, in which the promoters of the novel essential genes were replaced by the doxycycline‐regulated tetO7‐CYC1 promoter. This promoter is active in normal growth medium but results in downregulation of the gene in the presence of doxycycline. The yeast cells were grown in the presence or absence of doxycycline, and both the growth and secretion of the heat shock protein, Hsp150p, into the culture medium were determined. In seven strains there was a specific effect on protein secretion. In a strain in which the RPN5 gene was downregulated, the level of secreted Hsp150p was increased compared to the control culture. When RER2 was downregulated, cells secreted Hsp150p that was not of the mature size. In five strains, secretion was more severely reduced than cell growth. One of these downregulated genes, YGL098w, was recently reported to encode an ER‐located t‐SNARE, USE1. Four of the genes detected, NOG2, NOP15, RRP40 and SDA1, encode proteins involved in ribosome assembly, suggesting a possible new signalling pathway between ribosome biogenesis and production of secreted proteins. The results obtained here indicate that the present screen could be successfully used in larger scale to identify novel secretion‐related genes. Copyright © 2004 John Wiley & Sons, Ltd.
Functional analysis of the Candida albicans ALS1 gene product
Authors: Loza Lucio , Fu Yue , Ibrahim Ashraf S. , Sheppard Donald C. , Filler Scott G. , Edwards John E.
Published: April 2004

ALS1 encodes a cell surface protein that mediates adherence of Candida albicans to endothelial cells. The predicted Als1p has an N‐terminal region, which contains a signal peptide; a middle region, which contains 20 36‐amino acid tandem repeats; and a C‐terminal region, which contains a glycosylphosphotidylinositol‐anchorage sequence. We used site‐directed mutagenesis to delineate the regions in Als1p required for endothelial cell adherence and cell surface expression of the protein. Mutant alleles of ALS1 containing either deletions or insertions were expressed in the normally non‐adherent Saccharomyces cerevisiae. These transformants were analysed for endothelial cell adherence and cell surface expression of Als1p. We found that mutations centred around amino acid 285 in the N‐terminus completely abolished adherence, but had no effect on cell surface expression of Als1p. Deletion of 15 of the tandem repeats reduced adherence by 50%, whereas deletion of all abolished adherence completely, even though cell surface expression of the N‐terminus of Als1p was maintained. Insertions into the C‐terminus at amino acids 413 and 254 upstream of the stop codon resulted in a modest loss of adherence, while cell surface expression of Als1p was maintained. An insertion at amino acid 249 in the C‐terminus caused complete loss of both adherence and cell surface expression, even though the glycosylphosphotidylinositol‐anchorage sequence remained intact. These data suggest a model of Als1p in which the endothelial cell binding region is localized within its N‐terminus, the tandem repeats are essential for the proper presentation of the binding site, and the C‐terminus is required for localizing Als1p to the cell surface. Copyright © 2004 John Wiley & Sons, Ltd.
Interaction of 6‐phosphofructokinase with cytosolic proteins of Saccharomyces cerevisiae
Authors: Schwock Jörg , Kirchberger Jürgen , Edelmann Anke , Kriegel Thomas M. , Kopperschläger Gerhard
Published: April 2004

Hetero‐octameric 6‐phosphofructokinase (Pfk‐1) from Saccharomyces cerevisiae is composed of two types of subunits, α and β, which are encoded by the unlinked genes PFK1 and PFK2. Pfk single deletion mutants expressing only one type of subunit exhibit Pfk‐1 activity in vivo which, however, is completely lost immediately after cell disruption. In order to elucidate the preconditions of the in vivo activity of the mutant enzymes composed of either α‐ or β‐subunits, we have investigated their potential interaction with selected heat shock and cytoskeletal proteins, employing co‐immunoprecipitation and immunofluorescence microscopy. Western blot analysis identified the mitochondrial chaperonin Hsp60, as well as the cytoskeleton proteins α‐tubulin and actin, in complexes with Pfk‐1 that were co‐precipitated from a cell‐free extract of a pfk2 single deletion mutant expressing only the α‐subunit. The interaction of the corresponding mutant enzyme and Hsp60 was found to depend on the ATP concentration of the extract. Immunofluorescence microscopy displayed a conspicuously filamentous arrangement of the Pfk‐1 mutant protein, exclusively in the pfk2 single deletion mutant. The analysis of structure and activity of Pfk‐1 expressed in S. cerevisiae mutant strains defective in various heat shock proteins (TRiC/CCT, Hsp70, Hsp 104) and in the respective wild‐type background did not reveal significant differences. Copyright © 2004 John Wiley & Sons, Ltd.
Identification of genes encoding putative nucleoporins and transport factors in the fission yeast Schizosaccharomyces pombe: a deletion analysis
Authors: Chen Xue Qin , Du Xianming , Liu Jianhua , Balasubramanian Mohan K. , Balasundaram David
Published: April 2004

In a systematic approach to study genes that are related to nucleocytoplasmic trafficking in the fission yeast Schizosaccharomyces pombe, the open reading frames (ORFs) of 26 putative nucleoporins and transport factors were deleted. Here we report the initial characterization of these deletion mutants. Of the 26 putative genes deleted, 14 were found to be essential for viability. Null mutations of essential genes resulted in failure to either complete one round or to sustain cell division. Four of the 14 essential genes, SPBC582.11c, SPBC17G9.04c, SPBC3B9.16c and SPCC162.08c, encode putative nucleoporins and a myosin‐like protein with homologues NUP84, NUP85, NUP120 and MLP1, respectively, that are not required for viability in Saccharomyces cerevisiae, suggesting that their gene products perform critical functions in Sz. pombe. On the basis of combined drug sensitivity assays and genetic analysis we have identified five non‐essential null mutants that were hypersensitive to the microtubule depolymerizing drug thiabendazole (TBZ) and exhibited a cut phenotype upon TBZ treatment, suggesting possible involvement in microtubule function. Three of the corresponding ORFs, SPCC18B5.07c, nup40 and SPAC1805.04, encode putative nucleoporins with low similarity to the S. cerevisiae nucleoporins NUP2p, NUP53p and NUP133p, respectively. Further genetic analysis revealed that one of the nucleoporin genes, nup40, and another gene, SPCC1322.06, encoding a putative importin‐β/Cse1p superfamily protein may have a spindle checkpoint function. Copyright © 2004 John Wiley & Sons, Ltd.
Causes of mortality in captive cotton‐top tamarins (Saguinus oedipus)
Authors: Leong Kirsten M. , Terrell Scott P. , Savage Anne
Published: April 2004

Cotton‐top tamarins have been housed in captivity in the United States for over five decades. These animals initially were managed in biomedical and research facilities, and more recently have been kept in zoos as well. Although the causes of mortality in captive cotton‐top tamarins have been a topic of investigation for biomedical colonies, they have not been addressed for the North American zoo population. In this retrospective study we review the causes of mortality in the AZA Cotton‐top Tamarin Species Survival Plan (SSP)© population during 1997–2001 to assess current husbandry practices and assist in further developing effective husbandry and management programs for this endangered species. Zoo Biol 23:127–137, 2004. © 2004 Wiley‐Liss, Inc.
Monitoring stress in captive giant pandas (Ailuropoda melanoleuca): behavioral and hormonal responses to ambient noise
Authors: Owen Megan A. , Swaisgood Ronald R. , Czekala Nancy M. , Steinman Karen , Lindburg Donald G.
Published: April 2004

Anthropogenic noise may impact captive breeding programs for endangered species. We recorded ambient noise and monitored potential behavioral and hormonal indices of stress in two captive giant pandas for 4 years. Statistical analyses were conducted for each individual separately, which allowed us to generalize only to these two animals. These preliminary findings indicate that ambient noise can have long‐lasting effects on stress indices. Days characterized by louder levels of noise were associated with increased locomotion, restless manipulation of the exit door of the enclosure, increased scratching and vocalizations indicative of agitation, and/or increased glucocorticoids excreted in urine. These general effects were modulated by several factors: 1) Brief loud noise evoked behavioral distress, but not pituitary‐adrenal activation. More chronic, moderate‐amplitude noise was associated with higher levels of glucocorticoids. 2) Some responses were frequency‐dependent, with loud low‐frequency noise having the greatest impact. 3) Female reproductive condition interacted significantly with noise amplitude for all behavioral measures, with stronger effects for the loudest acute noises. The female appeared especially sensitive to noise during estrus and lactation, and less so during pregnancy/pseudopregnancy and nonreproductive periods. Despite these statistical effects, we found no compelling evidence that these adjustments indicate substantive detrimental effects on well‐being or reproduction. Nonetheless, careful monitoring of giant pandas and other captive‐held species is advisable, especially during reproductively sensitive periods such as implantation and birth. Zoo Biol 23:147‐164, 2004. © 2004 Wiley‐Liss, Inc.
Transportation techniques for massive scleractinian corals
Authors: Petersen Dirk , Laterveer Michaël , Bergen David van , Kuenen Maureen
Published: April 2004

Transportation techniques for scleractinian corals have been described mainly for fragments and small colonies. As part of a recent study on captive sexual reproduction of the Caribbean species Montastrea annularis and Diploria strigosa, we transported relatively large (max. diameter of 21 cm), heavy (max. weight of 9,200 g) colonies of both species from Curaçao, Netherlands Antilles, to Rotterdam, The Netherlands. A new transportation technology was applied whereby the corals were transplanted to specially designed PVC crosses to provide stabilization during transport. In two transports (November 2001 and February 2002), 100 colonies were transported submerged, in a shipping time of >35 hr. The survival rate measured 2 weeks after transport was 100%. Four and 8 months after transport, respectively, two colonies of D. strigosa died without any obvious cause. In November 2002 we observed an outbreak of Dark Spots disease (DSD) affecting two‐thirds of the colonies of M. annularis. Although the colonies did not show any symptoms when they were collected, the disease most probably was transferred when the coral were transported from the field to the laboratory. The presented method is appropriate for transporting large, heavy corals–especially for scientific purposes. In general, species‐specific properties, colony size, and transportation time determine which transportation method should be applied. In the future, there may be a shift toward transports of fragments, coral larvae, and primary polyps to reduce collections in the field. Zoo Biol 23:165–176, 2004. © 2004 Wiley‐Liss, Inc.
Comparative study on the growth of juvenile Galapagos giant tortoises (Geochelone nigra) at the Charles Darwin Research Station (Galapagos Islands, Ecuador) and Zoo Zurich (Zurich, Switzerland)
Authors: Furrer S.C. , Hatt J.M. , Snell H. , Marquez C. , Honegger R.E. , Rübel A.
Published: April 2004

In this study, the growth rates of a group of Galapagos giant tortoises raised in their natural habitat at the Charles Darwin Research Station (CDRS; Galapagos Islands, Ecuador) and a group of captive‐bred specimens (Zoo Zurich, Zurich, Switzerland) were compared for the first time. A great discrepancy in growth rates was observed after the first year. When the animals were 4 years old, the carapace in the Zurich specimens was approximately twice as long as that in the CDRS tortoises, and the Zurich animals weighed approximately 10 times more than the CDRS animals. The zoo diet was modified by a reduction in nutrients and an increase in fiber to produce a more natural growth rate. Zoo Biol 23:177‐183, 2004. © 2004 Wiley‐Liss, Inc.
A pathomechanical concept explains muscle loss and fatty muscular changes following surgical tendon release
Authors: Meyer Dominik C. , Hoppeler Hans , von Rechenberg Brigitte , Gerber Christian
Published: April 2004

Following tendon tear, the musculo‐tendinous unit retracts permanently, looses muscle fibre volume and is infiltrated with fat. This is currently considered to be an unexplained degenerative process. In a sheep model of chronic tendon tear with delayed tendon repair (35 weeks after tendon release), we studied the nature of these muscle changes in eight experimental animals. At sacrifice (75 weeks after tendon release) the muscle had retracted by 1.7±0.5 cm (9% of entire length, P < 0.0001), the pennation angle had increased from 22±2.5° to 50±11° (P < 0.0001) and the mean muscle fibre length had shortened from 32±3 to 16±5 mm (50%, P < 0.0001). In electron and light microscopy, we found essentially normal muscle fibres with an unaltered fibre diameter and myofibrillar structure, while interstitial fat and fibrous tissue had increased from 3.9% to 45.9% (P < 0.0001) of the muscle volume.

Geometric modelling showed that the increase of the pennation angle separates the muscle fibre bundles mechanically like limbs of a parallelogram. Infiltrating fat cells fill the created space between the reoriented muscle fibres which may be quantitatively calculated without affecting the structural properties of the muscle cells. Fatty infiltration is therefore not seen as a degenerative process but a necessary rearrangement of the tissue after macroarchitectural changes caused by musculo‐tendinous retraction. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
The efficiency and the conduct of European banks: Developments after 1992
Authors: Schure Paul , Wagenvoort Rien , O'Brien Dermot
Published: April 2004

We assess the efficiency of the European banking sector in the 5‐year period following the implementation of the Second Banking Directive of the European Union (EU). We first determine the degree of cost efficiency of EU banks in 1993–1997. After that, we explore to what extent efficient European banks are managed differently than their inefficient peers. Our datasets comprise 5 years of observations on 1347 savings and 873 commercial banks. We use the new recursive thick frontier approach (RTFA) method to establish our results. We find that structural factors, such as technological progress or increased bank competition, have lowered the cost base of banks by about 5% annually during the sample period. Managerial inability to control costs (X‐inefficiency) is with 17–25% the main source of bank inefficiency in the EU. Managerial efficiency varies a great deal within Europe, and there seems to be no tendency towards convergence. We find that small savings banks can exploit economies of scale. The EU savings bank sector would cut costs by about 3% if small savings banks merged.
On the time periodic thermistor problem
Authors: ALLEGRETTO WALTER , LIN YANPING , MA SHUQING
Published: April 2004

In this paper we study a nonlocal parabolic/elliptic system which models thermistor behaviour in cases where heat losses to the surrounding gas play a significant role. The existence of time periodic solutions for the system is established through Faedo-Galerkin approximations and the Leray–Schauder degree theory. We show that for the small gas pressure case, the temperature of the time periodic solutions is positive. Moreover we consider the long time behaviour of the system and prove the existence of a uniform attractor. Finally, the finite dimensionality of the attractor is discussed.
Multiplicity and stability of travelling wave solutions in a free boundary combustion-radiation problem
Authors: BACONNEAU OLIVIER , VAN DEN BERG JAN BOUWE , BRAUNER CLAUDE-MICHEL , HULSHOF JOSEPHUU
Published: April 2004

We study travelling wave solutions of a one-dimensional two-phase Free Boundary Problem, which models premixed flames propagating in a gaseous mixture with dust. The model combines diffusion of mass and temperature with reaction at the flame front, the reaction rate being temperature dependent. The radiative effects due to the presence of dust account for the divergence of the radiative flux entering the equation for temperature. This flux is modelled by the Eddington equation. In an appropriate limit the divergence of the flux takes the form of a nonlinear heat loss term. The resulting reduced model is able to capture a hysteresis effect that appears if the amount of fuel in front of the flame, or equivalently, the adiabatic temperature is taken as a control parameter.
The recursive record semantics of objects revisited
Authors: BOUDOL GÉRARD
Published: April 2004

In a call-by-value language, representing objects as recursive records requires using an unsafe fixpoint. We design, for a core language including extensible records, a type system which rules out unsafe recursion and still supports the construction of a principal type for each typable term. We illustrate the expressive power of this language with respect to object-oriented programming by introducing a sub-language for “mixin-based” programming.
Composition of functions with accumulating parameters
Authors: VOIGTLÄNDER JANIS , KÜHNEMANN ARMIN
Published: April 2004

Many functional programs with accumulating parameters are contained in the class of macro tree transducers. We present a program transformation technique that can be used to solve the efficiency problems due to creation and consumption of intermediate data structures in compositions of such functions, where classical deforestation techniques fail. To do so, given two macro tree transducers under appropriate restrictions, we construct a single macro tree transducer that implements the composition of the two original ones. The imposed restrictions are more liberal than those in the literature on macro tree transducer composition, thus generalising previous results.
Escape from Zurg: an exercise in logic programming
Authors: ERWIG MARTIN
Published: April 2004

In this Pearl we illustrate with an example that modern functional programming languages like Haskell can be used effectively for programming search problems, in contrast to the widespread belief that Prolog is much better suited for tasks like these.
Förderung des Transfers von Diagnosestrategien durch computergestütztes Training mit kognitiver Modellierung
Authors: Schaper Niclas , Hochholdinger Sabine , Sonntag Karlheinz
Published: April 2004

Zusammenfassung. Störungsdiagnose in komplexen Produktionssystemen stellt hohe Anforderungen an Mitarbeiter. Zur Vermittlung adäquater Diagnosestrategien wurde ein computergestütztes Training (CBT) mit einem Zusatzmodul zur kognitiven Modellierung eingesetzt, das Lerntransfer fördern soll. Mit 45 Auszubildenden in Mechatronik wurde das Trainingsmodul hinsichtlich Transferförderung evaluiert. Den Kern des CBTs bildet die Simulation einer teilautomatisierten Fertigungsanlage mit 20 Störungsdiagnoseaufgaben. Sechs Videos zur kognitiven Modellierung wurden als didaktische Elemente für die Vermittlung von Strategien zur systematischen Fehlersuche eingesetzt. Die Experimentalgruppe bearbeitete das Training mit, die Kontrollgruppe ohne kognitive Modellierung. Mit Hilfe von Diagnoseaufgaben auf drei Transferstufen wurden Effekte der kognitiven Modellierung auf den Erfolg der Fehlersuche erfasst. Außerdem wurde die diagnostische Problemlösestrategie anhand von Logfiles und Verhaltensbeobachtungen analysiert. In den ersten beiden Transferstufen war die Experimentalgruppe der Kontrollgruppe signifikant überlegen bezüglich Erfolgs- und Strategiemaßen, nicht jedoch bei Aufgaben mit dem höchsten Transferabstand.
Kognitiv-emotionale Prozesse als Auslöser von Innovationen
Authors: Krause Diana E.
Published: April 2004

Zusammenfassung. Vor dem Hintergrund der Vernachlässigung kognitiv-emotionaler Prozesse als Auslöser von Innovationen entwickelt dieser Beitrag auf der Basis der innovationskontextspezifisch adaptierten Lazarus-Theorie ein Modell, das das Zusammenwirken zwischen Kognitionen, Emotionen und innovationsbezogenen Verhaltensweisen von Führungskräften sowie den Innovationserfolg beschreibt. Es wird angenommen, dass positive und negative Emotionen, Innovationsverhalten (Ideengenerierung/-prüfung und Implementierung) und innovationshinderliche Verhaltensweisen (Flucht und intrapsychische Anpassung) von kombinierten Situationswahrnehmungen der Führungskräfte abhängen, wobei die wahrgenommene Veränderungsfähigkeit (Situationskontrolle) der betrieblichen Situation besonders bedeutsam ist. Ferner wird postuliert, dass die positiven und negativen Emotionen der Führungskräfte unmittelbare Effekte auf ihr Innovationsverhalten und ihre innovationshinderlichen Verhaltenweisen haben, wobei sich das Innovationsverhalten funktional auf den Innovationserfolg auswirkt, die innovationshinderlichen Verhaltensweisen hingegen erfolgsreduzierend wirken. In getrennten Felduntersuchungen ließen sich alle Konstruktunterscheidungen faktorenanalytisch bestätigen. Zur Überprüfung der Modellannahmen wurden bundesweit N = 399 Führungskräfte aus verschiedenen Organisationen und Branchen schriftlich befragt. Alle Modellannahmen werden durch Varianzanalysen und hierarchische Regressionsanalysen empirisch bestätigt.
Response of the Mediterranean Sea thermohaline circulation to observed changes in the winter wind stress field in the period 1980–1993
Authors: Samuel Sarah , Haines Keith , Josey Simon , Myers Paul G.
Published: April 2004

This paper seeks to model changes in deep water production in the eastern Mediterranean induced by changes in winter wind stress. An analysis of individual monthly wind stress fields over the Mediterranean for 1980–1993 from the SOC flux data set shows that an intensification of the winter mean (mainly January) wind stress over the Aegean Sea and Levantine basin occurred in the latter half of this period. A weakening of the Mistral occurred at the same time. Two monthly wind stress climatologies were created using the 1980–1987 and 1988–1993 periods, and these were used to force an ocean general circulation model of the Mediterranean, with climatological surface T, S relaxation. The Levantine intermediate water (LIW) dispersal path in the Ionian is altered in the 1988–1993 experiment with no pathway to the Adriatic and, consequently, greatly reduced exchange at Otranto and a collapse in Adriatic deep water formation. In contrast, there is an increased exchange of LIW at the Cretan arc straits and enhanced Aegean deep water production in the 1988–1993 experiment. Much more Aegean water exits into the Levantine and Ionian basins as is shown by an east‐west cross section south of Crete, along a similar path to the Meteor cruise in 1995. Changes in air‐sea fluxes are diagnosed from the model showing a small increase in wintertime cooling over the Aegean and reduced cooling over the Adriatic after 1987. While the changes in air‐sea fluxes are probably underrepresented by this simulation, the large changes induced by the wind forcing suggest this could be a mechanism in the altered thermohaline state of the eastern Mediterranean since 1987.
Growth of and brine drainage from NaCl‐H2O freezing: A simulation of young sea ice
Authors: Oertling Annette B. , Watts Robert G.
Published: April 2004

A numerical simulation is used to predict the early time evolution of the solidification and brine drainage of a binary NaCl‐H2O mixture. The mathematical formulation is based on continuum mixture theory as outlined by Bennon and Incropera [1987] and Medjani [1993]. Results yield a simple relationship between surface temperature and cumulative salt mass draining from the ice. Additionally, a scaling analysis of the energy equation leads to a simple parameterization for ice thickness. Results compare well with existing laboratory measurements; however, the delay in onset of brine drainage reported in the literature is not supported by these results. Images generated using continuum salinity and liquid fraction data, overlaid with streamlines generated from velocity data, provide a reasonable qualitative resemblance to laboratory observations of NaCl‐H2O ice growth.
Controls on moss evaporation in a boreal black spruce forest
Authors: Heijmans Monique M. P. D. , Arp Wim J. , Chapin F. Stuart
Published: April 2004

Mosses are an important component of the boreal forest, but little is known about their contribution to ecosystem carbon, water, and energy exchange. We studied the role of mosses in boreal forest evapotranspiration by conducting two experiments in a black spruce forest in Fairbanks, Alaska. Moss evaporation was measured using lysimeters filled with Hylocomium splendens or Sphagnum capillifolium. Microclimate and moisture content were varied by placing the lysimeters in different habitats (dense forest, open forest, bog), and by manipulating the water supply (no water, natural rainfall, water added). Moss evaporation rates between 1 June and 8 September averaged 0.3, 0.9, and 1.5 mm day−1 in the dense forest (Hylocomium), open forest (Hylocomium and Sphagnum), and bog (Sphagnum) respectively. Assuming a total forest evapotranspiration rate of 2 mm day−1, this study shows that moss evaporation contributes considerably to boreal black spruce forest evapotranspiration. Moss evaporation rates depended strongly on the openness of the forest and to a lesser degree on the density of the vascular plant canopy and on moss species. The strong influence of habitat suggests that microclimate is the primary factor determining moss evaporation rates. Hylocomium evaporation reacted strongly to experimental water additions, indicating that precipitation frequency is an important factor in addition to microclimate for this species. The large moss evaporation rates in this study suggest a potential cooling effect of mosses, of Sphagnum in particular.