bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening decreases prostate cancer mortality: 11‐year follow‐up of the 1988 Quebec prospective randomized controlled trial
Authors: Labrie Fernand , Candas Bernard , Cusan Lionel , Gomez Jose Luis , Bélanger Alain , Brousseau G. , Chevrette Eric , Lévesque Jacques 
Published: March 2004

AbstractPURPOSEThis clinical trial is aimed at evaluating the impact of prostate cancer screening on cancer‐specific mortality.SUBJECTS AND METHODSForty‐six thousand four hundred and eighty‐six (46,486) men aged 45–80 years registered in the electoral roll of the Quebec city area were randomized in 1988 between screening and no screening. Screening included measurement of serum prostatic specific antigen (PSA) using 3.0 ng/ml as upper limit of normal and digital rectal examination (DRE) at first visit. At follow‐up visits, serum PSA only was used.RESULTSSeventy‐four (74) deaths from prostate cancer occurred in the 14,231 unscreened controls while 10 deaths were observed in the screened group of 7,348 men during the first 11 years following randomization. Median follow‐up of screened men was 7.93 years. A Cox proportional hazards model of the age at death from prostate cancer shows a 62% reduction (P < 0.002, Fisher's exact test) of cause‐specific mortality in the screened men (P = 0.005). These results are in agreement with the continuous decrease of prostate cancer mortality observed in North America. © 2004 Wiley‐Liss, Inc.
Partitioning tracer tests as a remediation metric: Case study at naval amphibious base little creek, Virginia Beach, Virginia
Authors: Divine Craig E. , McCray John E. , Wolf Martin Leah M. , Blanford William J. , Blitzer David J. , Brusseau Mark L. , Boving Thomas B. 
Published: March 2004

AbstractThe partitioning tracer test (PTT) is a characterization tool that can be used to quantify the
porespace saturation (SN) and spatial distribution of dense nonaqueous phase liquids
(DNAPLs) in the subsurface. Because the method essentially eliminates data interpolation errors by
directly measuring a relatively large subsurface volume, it offers significant promise as a remediation metric
for DNAPL‐zone remediation efforts. This article presents, in detail, the design and results of field
PTTs conducted before and after a DNAPL‐zone treatment at the Naval Amphibious Base Little Creek,
Virginia Beach, Virginia. The results from different tracers yield a relatively large range in SN
estimates, indicating notable uncertainty and presenting significant challenges for meaningful interpretation.
Several potential interpretation methods are presented, resulting in an estimated DNAPL removal range of 15 to
109 L. While this range is large, it is consistent with the DNAPL removal (∼30 L) determined from
analysis of effluent concentration measurements collected during the remediation efforts. At this site, the
initial and final SN values are low, and the relatively inconsistent performance of the various
tracers indicates that these levels are near the lower practical quantification limit for these PTTs;
however, the effective lower quantification limit for these tests is unknown. Generally, an understanding of
lower quantification limits is particularly important for interpretation of post‐remediation PTTs because
SN values are likely to be low (due to remediation efforts) and the SN estimated
from the PTT may be used to predict long‐term dissolved plume behavior and assess associated
environmental risk. Partitioning tracer test quantification limits are test‐specific, as they are
dependent on a variety of factors including analytical uncertainty, tracer breakthrough characteristics, and
tracer data integration techniques. The results of this case study indicate that methods for estimating lower
quantification limits for field PTTs require further development. © 2004 Wiley Periodicals, Inc.
Identification of potential cell‐surface proteins in Candida albicans and investigation of the role of a putative cell‐surface glycosidase in adhesion and virulence
Authors: Alberti‐Segui Christine , Morales Arturo J. , Xing Heming , Kessler Marco M. , Willins Debra Aker , Weinstock Keith G. , Cottarel Guillaume , Fechtel Kim , Rogers Bruce 
Published: March 2004

AbstractCell‐surface proteins are attractive targets for the development of novel antifungals as they are more accessible to drugs than are intracellular targets. By using a computational biology approach, we identified 180 potential cell‐surface proteins in Candida albicans, including the known cell‐surface adhesin Als1 and other cell‐surface antigens, such as Pra1 and Csa1. Six proteins (named Csf1‐6 for cell‐surface factors) were selected for further biological characterization. First, we verified that the selected CSF genes are expressed in the yeast and/or hyphal form and then we investigated the effect of the loss of each CSF gene on cell‐wall integrity, filamentation, adhesion to mammalian cells and virulence. As a result, we identified Csf4, a putative glycosidase with an apparent orthologue in Saccharomyces cerevisiae (Utr2), as an important factor for cell‐wall integrity and maintenance. Interestingly, deletion of CSF4 also resulted in a defect in filamentation, a reduction in adherence to mammalian cells in an in vitro adhesion assay, and a prolongation of survival in an immunocompetent mouse model of disseminated candidiasis. A delay in colonization of key organs (e.g. kidney) was also observed, which is consistent with a reduction in virulence of the csf4‐deletion strain. These data indicate a key role for extracellular glycosidases in fungal pathogenesis and represent a new site for therapeutic intervention to cure and prevent fungal disease. Copyright © 2004 John Wiley & Sons, Ltd.
Expression of a plant serine O‐acetyltransferase in Saccharomyces cerevisiae confers osmotic tolerance and creates an alternative pathway for cysteine biosynthesis
Authors: Mulet Jose M. , Alemany Beatriz , Ros Roc , Calvete Juan J. , Serrano Ramon 
Published: March 2004

AbstractScreening of a sugar beet (Beta vulgaris cv. Dita) cDNA library for clones able to confer osmotic tolerance to the osmosensitive gpd1 mutant of Saccharomyces cerevisiae identified a novel serine O‐acetyltransferase (BvSAT; EC 2.3.1.30). This enzyme is involved in cysteine biosynthesis in plants and bacteria, producing O‐acetylserine, which is converted into cysteine in a reaction catalysed by O‐acetylserine sulphydrylase (EC 4.2.99.8). This pathway is not conserved in yeast, where cysteine is synthesized in a four‐step pathway starting with homoserine and having O‐acetylhomoserine, homocysteine and cystathionine as intermediates. Expression of BvSAT in yeast takes advantage of the activity of yeast O‐acetylhomoserine sulphydrylase (MET15/MET17/MET25; EC 4.2.99.10) with O‐acetylserine as substrate and induces an alternative cysteine biosynthesis pathway. Our results imply that the resulting increase in cysteine production confers enhanced resistance against osmotic stress in the osmosensitive yeast strain. These data demonstrate that cysteine biosynthesis is a limiting factor in osmotic stress tolerance in yeast. Copyright © 2004 John Wiley & Sons, Ltd.
Isolation of an acetyl‐CoA synthetase gene (ZbACS2) from Zygosaccharomyces bailii
Authors: Rodrigues Fernando , Zeeman Anne‐Marie , Cardoso Helena , Sousa Maria João , Steensma H. Yde , Côrte‐Real Manuela , Leão Cecília 
Published: March 2004

AbstractA gene homologous to Saccharomyces cerevisiae ACS genes, coding for acetyl‐CoA synthetase, has been cloned from the yeast Zygosaccharomyces bailii ISA 1307, by using reverse genetic approaches. A probe obtained by PCR amplification from Z. bailii DNA, using primers derived from two conserved regions of yeast ACS proteins, RIGAIHSVVF (ScAcs1p; 210–219) and RVDDVVNVSG (ScAcs1p; 574–583), was used for screening a Z. bailii genomic library. Nine clones with partially overlapping inserts were isolated. The sequenced DNA fragment contains a complete ORF of 2027 bp (ZbACS2) and the deduced polypeptide shares significant homologies with the products of ACS2 genes from S. cerevisiae and Kluyveromyces lactis (81% and 82% identity and 84% and 89% similarity, respectively). Phylogenetic analysis shows that the sequence of Zbacs2 is more closely related to the sequences from Acs2 than to those from Acs1 proteins. Moreover, this analysis revealed that the gene duplication producing Acs1 and Acs2 proteins has occurred in the common ancestor of S. cerevisiae, K. lactis, Candida albicans, C. glabrata and Debaryomyces hansenii lineages. Additionally, the cloned gene allowed growth of S. cerevisiae Scacs2 null mutant, in medium containing glucose as the only carbon and energy source, indicating that it encodes a functional acetyl‐CoA synthetase. Also, S. cerevisiae cells expressing ZbACS2 have a shorter lag time, in medium containing glucose (2%, w/v) plus acetic acid (0.1–0.35%, v/v). No differences in cell response to acetic acid stress were detected both by specific growth and death rates. The mode of regulation of ZbACS2 appears to be different from ScACS2 and KlACS2, being subject to repression by a glucose pulse in acetic acid‐grown cells. The nucleotide sequence of a common 5269 bp fragment has been deposited in the EMBL Data Library under Accession No. AJ314837. Copyright © 2004 John Wiley & Sons, Ltd.
GFP as a quantitative reporter of gene regulation in Candida albicans
Authors: Barelle Caroline J. , Manson Claire L. , MacCallum Donna M. , Odds Frank C. , Gow Neil A. R. , Brown Alistair J. P. 
Published: March 2004

AbstractA system has been developed for the quantitative analysis of gene expression within individual Candida albicans cells in infected tissue. The system is based on the plasmid pGFP, which contains the codon‐optimized yeast enhanced green fluorescent protein (yEGFP; Cormack et al., 1997) cloned between a basal CaADH1 promoter and the ScCYC1 terminator on an integrating vector. Promoters were inserted into pGFP and GFP levels measured in individual cells by quantitative fluorescence microscopy. Analysis of pPCK1–GFP and pMET3–GFP fusions revealed that GFP folds rapidly following gene induction, and is turned over rapidly following gene repression. Hence, single cell fluorescence measurements are likely to reflect ongoing gene expression levels with reasonable accuracy. pACT1–GFP expression levels were relatively constant during growth of C. albicans in both yeast and hyphal forms, and during growth in vivo in the mouse model of systemic infection. Therefore, pACT1–GFP provides a useful control for this quantitative GFP‐based system in future analyses of C. albicans molecular responses during fungal infections. Copyright © 2004 John Wiley & Sons, Ltd.
The Saccharomyces cerevisiae alcohol acetyl transferase Atf1p is localized in lipid particles
Authors: Verstrepen Kevin J. , Van Laere Stijn D. M. , Vercammen Jo , Derdelinckx Guy , Dufour Jean‐Pierre , Pretorius Isak S. , Winderickx Joris , Thevelein Johan M. , Delvaux Freddy R. 
Published: March 2004

AbstractThe yeast alcohol acetyl transferase I, Atf1p, is responsible for the major part of volatile acetate ester production in fermenting Saccharomyces cerevisiae cells. Some of these esters, such as ethyl acetate and isoamyl acetate, are important for the fruity flavours of wine, beer and other fermented beverages. In order to reveal the subcellular localization of Atf1p and further unravel the possible physiological role of this protein, ATF1::GFP fusion constructs were overexpressed in brewer's yeast. The transformant strain showed a significant increase in acetate ester formation, similar to that of an ATF1 overexpression strain, indicating that the Atf1p–GFP fusion protein was active. UV fluorescence microscopy revealed that the fusion protein was localized in small, sphere‐like organelles. These organelles could be selectively stained by the fluorescent dye Nile red, indicating that they contained high amounts of neutral lipids and/or sterols, a specific characteristic of yeast lipid particles. Purification of lipid particles from wild type and ATF1 deletion cells confirmed that the Atf1p–GFP fusion protein was located in these organelles. Furthermore, a clear alcohol acetyl transferase activity could be measured in the purified lipid particles of both wild type and transformed cells. The localization of Atf1p in lipid particles may indicate that Atf1p has a specific role in the lipid and/or sterol metabolism that takes place in these particles. Copyright © 2004 John Wiley & Sons, Ltd.
Alcohol dehydrogenases that catalyse methyl formate synthesis participate in formaldehyde detoxification in the methylotrophic yeast Candida boidinii
Authors: Yurimoto Hiroya , Lee Bumjun , Yasuda Fumi , Sakai Yasuyoshi , Kato Nobuo 
Published: March 2004

AbstractMethyl formate synthesis during growth on methanol by methylotrophic yeasts has been considered to play a role in formaldehyde detoxification. An enzyme that catalyses methyl formate synthesis was purified from methylotrophic yeasts, and was suggested to belong to a family of alcohol dehydrogenases (ADHs). In this study we report the gene cloning and gene disruption analysis of three ADH‐encoding genes in the methylotrophic yeast Candida boidinii (CbADH1, CbADH2 and CbADH3) in order to clarify the physiological role of methyl formate synthesis. From the primary structures of these three genes, CbAdh1 was shown to be cytosolic and CbAdh2 and CbAdh3 were mitochondrial enzymes. Gene products of CbADH1, CbADH2 and CbADH3 expressed in Escherichia coli showed both ADH‐ and methyl formate‐synthesizing activities. The results of gene‐disruption analyses suggested that methyl formate synthesis was mainly catalysed by a cytosolic ADH (CbAdh1), and this enzyme contributed to formaldehyde detoxification through glutathione‐independent formaldehyde oxidation during growth on methanol by methylotrophic yeasts. The GenBank/EMBL/DDBJ Accession Nos for CbADH1, CbADH2 and CbADH3 are AB125900, AB125901 and AB125902, respectively. Copyright © 2004 John Wiley & Sons, Ltd.
Mechanical environment alters tissue formation patterns during fracture repair
Authors: Smith‐Adaline E. A. , Volkman S. K. , Ignelzi M. A. , Slade J. , Platte S. , Goldstein S. A. 
Published: March 2004

AbstractFracture repair has previously been shown to be sensitive to mechanical environment, yet the specific relationship between strain character, magnitude and frequency, as well as other mechanical parameters, and tissue formation is not well understood. This study aimed to correlate strain distribution within the healing fracture gap with patterns of tissue formation using a rat model of a healing osteotomy subject to mechanical stimulation in bending. Finite element models based on realistic tissue distributions were used to estimate both the magnitude and spatial distribution of strains within the fracture gap. The spatial distribution of regenerating tissue was determined by microcomputed tomography and histology, and was confirmed using reverse transcription‐polymerase chain reaction (RT‐PCR). Results suggest that tensile strains suppress chondrogenesis during the mechanical stimulation period. After stimulation ends, however, tensile strains increased chondrogenesis followed by rapid bone formation. In contrast, in compressive environments, bone is formed primarily via intramembranous ossification. Taken together, these results suggest that intermittent tensile strains during fracture repair stimulate endochondral ossification and promote eventual bone healing compared to intermittent compressive strains and unstimulated fractures. Further understanding of these relationships may allow proposal of optimal therapeutic strategies for improvement of the fracture repair process. © 2004 Orthopaedic Research Society. Published y Elsevier Ltd. All rights reserved.
Omic space: coordinate-based integration and analysis of genomic phenomic interactions
Authors: Toyoda Tetsuro , Wada Akiyoshi 
Published: March 2004

Abstract
Motivation: With the recent progress in genomics, various data sets of omic interactions describing networks of omic elements have become available. In order to obtain reliable hypotheses from the data, it is effective to integrate interactions from different sorts of data sets. In order to facilitate a coordinate-based integration and analysis of omic interactions, we introduce the concept of an omic space comprising a comprehensive set of omic planes. Genomic, transcriptomic, proteomic, metabolomic, phenomic and other omic planes are defined by two orthogonal genomic-coordinate axes.
Results: We show that the omic space concept helps us to assimilate biological findings comprehensively into hypotheses or models combining higher-order phenomena and lower-order mechanisms by demonstrating that a comprehensive ranking of correspondences among interactions in the space can be used effectively for estimating candidates of responsible gene pairs for epistatic interacting loci of tumors in mice. We also show that the omic space offers a convenient framework for database integration, by presenting a system named the ‘Genome ⇔ Phenome Superhighway’ (GPS) that serves as a framework for integration and visualization of omic interactions based on omic spaces of some model species including Homo sapiens, Mus musculus, Caenorhabditis elegans and Arabidopsis thaliana.
Availability: For the GPS web site, see http://omicspace.riken.jp/gps/.
Inferring dynamic architecture of cellular networks using time series of gene expression, protein and metabolite data
Authors: Sontag Eduardo , Kiyatkin Anatoly , Kholodenko Boris N. 
Published: March 2004

Abstract
Motivation: High-throughput technologies have facilitated the acquisition of large genomics and proteomics datasets. However, these data provide snapshots of cellular behavior, rather than help us reveal causal relations. Here, we propose how these technologies can be utilized to infer the topology and strengths of connections among genes, proteins and metabolites by monitoring time-dependent responses of cellular networks to experimental interventions.
Results: We demonstrate that all connections leading to a given network node, e.g. to a particular gene, can be deduced from responses to perturbations none of which directly influences that node, e.g. using strains with knock-outs to other genes. To infer all interactions from stationary data, each node should be perturbed separately or in combination with other nodes. Monitoring time series provides richer information and does not require perturbations to all nodes. Overall, the methods we propose are capable of deducing and quantifying functional interactions within and across cellular gene, signaling and metabolic networks.
Supplementary Information: Supplementary material is available at http://www.dbi.tju.edu/bioinformatics2004.pdf
Long-term Effects of Different Humidification Systems on Endotracheal Tube Patency
Authors: Jaber Samir , Pigeot Jérôme , Fodil Redouane , Maggiore Salvatore , Harf Alain , Isabey Daniel , Brochard Laurent , Louis Bruno 
Published: March 2004

Background
Accumulation of mucous secretions in an endotracheal tube (ETT) increases its resistance, and the amount of deposit may be affected by the quality of humidification and heating of the inspired gas.

Methods
The authors assessed the impact of two humidification systems, a heated humidifier (HH) and a hygroscopic-hydrophobic heat and moisture exchanger (HME), on the ETT patency in patients selected to require mechanical ventilation for more than 48 h. This comparison was performed over two consecutive periods and used the acoustic reflection method, which characterizes the amount and site of ETT obstruction and allows estimating ETT inner volume and resistance. Measurements were performed three times a week over the period of mechanical ventilation. Comparisons were performed at mid duration and at the end of the mechanical ventilation period.

Results
The HH was used in 34 patients, and the HME was used in 26 patients. The two groups had similar severity and duration of mechanical ventilation. At mid duration of mechanical ventilation (5.5 +/- 3.3 vs. 4.8 +/- 3.3 days; P = 0.4), no difference was observed in ETT volume and resistance between the two groups. At the end of the study period (10.5 +/- 5.8 vs. 9.6 +/- 6.3 days of mechanical ventilation; P = 0.4), ETT volume was reduced to a greater extent with HME than with HH (-3.3 +/- 2.9 vs. -5.1 +/- 2.5%; P = 0.008), and ETT resistance increased significantly more with the HME than with the HH (8.4 +/- 12.2 vs. 19.4 +/- 17.7%; P = 0.001).

Conclusion
Prolonged use of humidification systems results in progressive reduction of ETT patency, and to a greater extent with HMEs than with HHs.
Histomorphologic Examination of Skeletal Muscle Preparations Does Not Differentiate between Malignant Hyperthermia–Susceptible and –Normal Patients
Authors: von Breunig Franziska , Wappler Frank , Hagel Christian , von Richthofen Verena , Fiege Marko , Weisshorn Ralf , Stavrou Dimitrios , Schulte am Esch Jochen 
Published: March 2004

Background
It has been suggested that malignant hyperthermia (MH) can be diagnosed by specific myopathologic alterations. The purpose of this study was to investigate whether there are characteristic myopathologic changes in skeletal muscles of MH-susceptible (MHS) compared with MH-normal (MHN) patients.

Methods
Four hundred forty patients with clinical suspicion of MH were classified as MHN, MH equivocal (MHE), or MHS by the in vitro contracture test with halothane and caffeine. In addition, a small muscle sample excised from each patient was analyzed by histologic, histochemical, immunohistochemical, and computer-aided morphometric methods.

Results
MHN was diagnosed in 243 patients, MHE was diagnosed in 65, and MHS was diagnosed in 132. No myopathologic abnormalities were found in 53.5% of the MHN, 53.9% of the MHE, and 56.1% of the MHS patients. Thirty-five percent of all patients showed one, 9.8% showed two, and only 0.9% showed three different pathologic findings within skeletal muscle preparations. The frequency of pathologic findings did not differ between the MHN and the MHS patients; only fiber type I predominance was observed more often in MHN. MHE patients could not be assigned to a diagnostic group by detection of myopathologic alterations. In six clinically unaffected patients, a former unrecognized myopathy, such as central core disease, was diagnosed. This disease is characterized by a specific alteration (cores).

Conclusions
Histologic differences between MHS and MHN statuses could not be demonstrated in this study. Histopathologic examinations can neither improve the diagnosis of MH nor contribute to a better definition of the MH status. However, histopathologic examinations might be useful to detect formerly unrecognized specific myopathies.