bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of coefficients to consider the incidences of hidden uncertainties
Authors: Bignoli A.J. 
Published: October 2004

AbstractLinguistic qualifications of hidden uncertainties of literary variables appear at the beginning of the Structural Codes. These literary variables (like “care of designer”, “capacity of builder”, etc.) have influences on the numerical values of classical variables defined in the codes (like “resistance”, “areas of reinforcement”, “depth of sections”, “loads”, etc. An attempt is made in this paper to transform the subjectively linguistic qualifications of literary variables to numerical values assessed by calculus using fuzzy arithmetic and fuzzy logic. To reach this target all qualifications of linguistic variables are given using fuzzy numbers established in two scales and chosen by consensus of experts. These qualifications are transformed into coefficients by “filtering” using the filters also established by consensus of experts. For classical variables considered “pro‐safety” PS and “anti‐safety” AS two different types of the coefficients are considered and, as a consequence, two different types of filters are used. Also maximum values of AS (anti‐safety) and minimum values of PS (pro‐safety) of the coefficients are given. Considerations on sensitivity of the approach due to subjectivity are made.
An uncertainty model of structural reliability with imprecise parameters of probability distributions
Authors: Utkin L.V. 
Published: October 2004

AbstractAn approach to compute bounds for the structural reliability by imprecise parameters of the stress and strength probability distributions is proposed. The approach is based on using imprecise probability theory and takes into account different types of independence of the stress, strength and their parameters. It is shown that computation of the imprecise stress‐strength model can be reduced to solution of a number of linear programming problems. Special cases of the exponentially distributed stress and strength are considered. Various numerical examples illustrate the approach and show the impact of the independence conditions on imprecision of results.
Fuzzy information and imprecise probability
Authors: Viertl R. , Hareter D. 
Published: October 2004

AbstractThere are different kinds of uncertainty in connection with statistics and probability models. Besides the fuzziness of data also the imprecision of a‐priori distributions is an essential feature of stochastic models in applied mathematical work. The paper is on statistical analysis for fuzzy data, fuzzy densities and its application in Bayesian inference, including a gereralized probability concept, called fuzzy probability distributions.
Fuzzy randomness – a contribution to imprecise probability
Authors: Möller B. 
Published: October 2004

AbstractThe formal description of data uncertainty as fuzzy randomness combines randomness and fuzziness in an uncertain model. This generalized uncertainty model permits the simultaneous consideration of randomness, fuzziness and fuzzy randomness. Variables and functions with the property of fuzzy randomness are introduced. The formulation of the latter using α‐levels and fuzzy bunch parameters permits the application of fuzzy randomness in the numerical simulation of engineering problems. The finite element method is extended by the inclusion of fuzzy randomness to yield the fuzzy stochastic finite element method (FSFEM). Examples demonstrate the advantage of the chosen formal description in practical applications.
Anti-apoptotic protein Bcl-2 interacts with and destabilizes the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA)
Authors: DREMINA Elena S. , SHAROV Victor S. , KUMAR Keshava , ZAIDI Asma , MICHAELIS Elias K. , SCHÖNEICH Christian 
Published: October 2004

The anti-apoptotic effect of Bcl-2 is well established, but the detailed mechanisms are unknown. In the present study, we show in vitro a direct interaction of Bcl-2 with the rat skeletal muscle SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase), leading to destabilization and inactivation of the protein. Recombinant human Bcl-2Δ21, a truncated form of Bcl-2 with a deletion of 21 residues at the C-terminal membrane-anchoring region, was expressed and affinity-purified as a glutathione S-transferase fusion protein. Bcl-2Δ21 co-immunoprecipitated and specifically interacted with SERCA in an in vitro-binding assay. The original level of Bcl-2 in sarcoplasmic reticulum vesicles was very low, i.e. hardly detectable by immunoblotting with specific antibodies. The addition of Bcl-2Δ21 to the sarcoplasmic reticulum resulted in the inhibition of the Ca2+-ATPase activity dependent on the Bcl-2Δ21/SERCA molar ratio and incubation time. A complete inactivation of SERCA was observed after 2.5 h of incubation at approx. 2:1 molar ratio of Bcl-2Δ21 to SERCA. In contrast, Bcl-2Δ21 did not significantly change the activity of the plasma-membrane Ca2+-ATPase. The redox state of the single Cys158 residue in Bcl-2Δ21 and the presence of GSH did not affect SERCA inhibition. The interaction of Bcl-2Δ21 with SERCA resulted in a conformational transition of SERCA, assessed through a Bcl-2-dependent increase in SERCA thiols available for the labelling with a fluorescent reagent. This partial unfolding of SERCA did not lead to a higher sensitivity of SERCA towards oxidative inactivation. Our results suggest that the direct interaction of Bcl-2 with SERCA may be involved in the regulation of apoptotic processes in vivo through modulation of cytoplasmic and/or endoplasmic reticulum calcium levels required for the execution of apoptosis.
Protein arginine methylation during lytic adenovirus infection
Authors: KZHYSHKOWSKA Julia , KREMMER Elisabeth , HOFMANN Markus , WOLF Hans , DOBNER Thomas 
Published: October 2004

Arginine methylation of proteins affects major processes in the cell, including transcriptional regulation, mRNA metabolism, signal transduction and protein sorting. Arginine methylation of Ad (adenovirus) E1B 55-kDa-associated protein E1B-AP5 was recently described by us [Kzhyshkowska, Schutt, Liss, Kremmer, Stauber, Wolf and Dobner (2001) Biochem. J. 358, 305–314]. In this first example of protein arginine methylation analysis in Ad-infected cells, we investigated methylation of the E1B-AP5 and the viral L4-100 kDa protein. We demonstrate that E1B-AP5 methylation is enhanced during the course of infection in a cell-type-specific manner. We also show that L4-100 kDa is efficiently methylated in Ad-infected cells. L4-100 kDa formed complex with methyltransferase in vivo during productive infection, and can be methylated by HRMT1L2 (human protein arginine methyltransferase 1) in vitro. Comparative analysis of E1B-AP5 and L4-100 kDa protein methylation in Ad-infected HeLa, MCF-7 and H1299 cells revealed that the profile of protein arginine methylation correlates with the efficiency of Ad proteins production. Our results suggest that protein arginine methylation is an important host-cell function required for efficient Ad replication.
Roles of USF, Ikaros and Sp proteins in the transcriptional regulation of the human reduced folate carrier B promoter
Authors: LIU Mingjun , WHETSTINE Johnathan R. , PAYTON Scott G. , GE Yubin , FLATLEY Robin M. , MATHERLY Larry H. 
Published: October 2004

The hRFC (human reduced folate carrier) is ubiquitously but differentially expressed in human tissues and its levels are regulated by up to seven non-coding regions (A1, A2, A, B, C, D and E) and at least four promoters. For the hRFC-B basal promoter, regulation involves binding of Sp (specificity protein) transcription factors to a critical GC-box. By transiently transfecting HT1080 cells with 5′- and 3′-deletion constructs spanning 1057 bp of upstream sequence, a transcriptionally important region was localized to 158 bp flanking the transcriptional start sites. By gel shift and chromatin immunoprecipitation assays, USF (upstream stimulatory factor), Sp1 and Ikaros-related proteins were bound to consensus elements (one E-box, two GC-box and three Ikaros) within this region. The functional importance of these elements was confirmed by transient tranfections of HT1080 cells with hRFC-B reporter constructs in which they were mutated, and by co-transfections of Drosophila Mel-2 cells with wild-type hRFC-B promoter and expression constructs for USF1, USF2a, Sp1 and Ikaros 2 and 8. Both USF1 and Sp1 proteins transactivated the hRFC-B promoter. Sp1 combined with USF1 resulted in a synergistic transactivation. Identical results were obtained with USF2a. Ikaros 2 was a repressor of hRFC-B promoter activity whose effects were partly reversed by the dominant-negative Ikaros 8. In HT1080 cells, transfection with Ikaros 2 decreased endogenous hRFC-B transcripts, whereas USF1 and Sp1 increased transcript levels. Ikaros 2 also decreased reporter gene activity and levels of acetylated chromatin associated with the endogenous promoter. Collectively, these results identify transcriptionally important regions in the hRFC-B promoter that include multiple GC-box, Ikaros and E-box elements. Our results also suggest that co-operative interactions between transcription factors Sp1 and USF are essential for high-level hRFC-B transactivation and imply that these effects are modulated by the family of Ikaros proteins and by histone acetylation.
The human multidrug-resistance-associated protein MRP1 mediates ATP-dependent transport of unconjugated bilirubin
Authors: RIGATO Igino , PASCOLO Lorella , FERNETTI Cristina , OSTROW J. Donald , TIRIBELLI Claudio 
Published: October 2004

Results of previous studies have suggested that UCB (unconjugated bilirubin) may be transported by MRP1/Mrp1 (multidrug-resistance-associated protein 1). To test this hypothesis directly, [3H]UCB transport was assessed in plasma-membrane vesicles from MDCKII cells (Madin–Darby canine kidney II cells) stably transfected with human MRP1 or MRP2; wild-type MDCKII cells served as controls. As revealed by Western blotting, transfection achieved abundant expression of MRP1 and MRP2. [3H]UCB uptake was measured in the presence of 60 μM human serum albumin at a free (unbound) concentration of UCB (BF) ranging from 5 to 72 nM and in the presence of 3 mM ATP or 3 mM AMP-PCP (adenosine 5′-[β,γ-methylene]triphosphate). MRP1-transfected vesicles showed transport activity three and five times higher respectively compared with MRP2 or wild-type vesicles, whose transport did not differ significantly. [3H]UCB transport was stimulated 4-fold by 1.5 mM GSH, occurred into an osmotically sensitive space, was inhibited by 3 μM MK571 and followed saturative kinetics with Km=10±3 nM (BF) and Vmax=100±13 pmol·min−1·(mg of protein)−1. UCB significantly inhibited the transport of LTC4 (leukotriene C4), a leukotriene substrate known to have high affinity for MRP1. Collectively, these results prove directly that MRP1 mediates ATP-dependent cellular export of UCB and supports its role in protecting cells from bilirubin toxicity.
Opposing actions of cellular retinol-binding protein and alcohol dehydrogenase control the balance between retinol storage and degradation
Authors: MOLOTKOV Andrei , GHYSELINCK Norbert B. , CHAMBON Pierre , DUESTER Gregg 
Published: October 2004

Vitamin A homoeostasis requires the gene encoding cellular retinol-binding protein-1 (Crbp1) which stimulates conversion of retinol into retinyl esters that serve as a storage form of vitamin A. The gene encoding alcohol dehydrogenase-1 (Adh1) greatly facilitates degradative metabolism of excess retinol into retinoic acid to protect against toxic effects of high dietary vitamin A. Crbp1−/−/Adh1−/− double mutant mice were generated to explore whether the stimulatory effect of CRBP1 on retinyl ester formation is due to limitation of retinol oxidation by ADH1, and whether ADH1 limits retinyl ester formation by opposing CRBP1. Compared with wild-type mice, liver retinyl ester levels were greatly reduced in Crbp1−/− mice, but Adh1−/− mice exhibited a significant increase in liver retinyl esters. Importantly, relatively normal liver retinyl ester levels were restored in Crbp1−/−/Adh1−/− mice. During vitamin A deficiency, the additional loss of Adh1 completely prevented the excessive loss of liver retinyl esters observed in Crbp1−/− mice for the first 5 weeks of deficiency and greatly minimized this loss for up to 13 weeks. Crbp1−/− mice also exhibited increased metabolism of a dose of retinol into retinoic acid, and this increased metabolism was not observed in Crbp1−/−/Adh1−/− mice. Our findings suggest that opposing actions of CRBP1 and ADH1 enable a large fraction of liver retinol to remain esterified due to CRBP1 action, while continuously allowing some retinol to be oxidized to retinoic acid by ADH1 for degradative retinoid turnover under any dietary vitamin A conditions.
Dual sensitivity of sarcoplasmic/endoplasmic Ca2+-ATPase to cytosolic and endoplasmic reticulum Ca2+ as a mechanism of modulating cytosolic Ca2+ oscillations
Authors: YANO Kojiro , PETERSEN Ole H. , TEPIKIN Alexei V. 
Published: October 2004

The effects of ER (endoplasmic reticulum) Ca2+ on cytosolic Ca2+ oscillations in pancreatic acinar cells were investigated using mathematical models of the Ca2+ oscillations. We first examined the mathematical model of SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase) to reproduce the highly co-operative inhibitory effect of Ca2+ in the ER lumen on ER Ca2+ uptake in the acinar cells. The model predicts that luminal Ca2+ would most probably inhibit the conversion of the conformation state with luminal Ca2+-binding sites (E2) into the conformation state with cytoplasmic Ca2+-binding sites (E1). The SERCA model derived from this prediction showed dose–response relationships to cytosolic and luminal Ca2+ concentrations that were consistent with the experimental data from the acinar cells. According to a mathematical model of cytosolic Ca2+ oscillations based on the modified SERCA model, a small decrease in the concentration of endoplasmic reticulum Ca2+ (approx. 20% of the total) was sufficient to abolish the oscillations. When a single type of IP3R (IP3 receptor) was included in the model, store depletion decreased the spike frequency. However, the frequency became less sensitive to store depletion when we added another type of IP3R with higher sensitivity to the concentration of free Ca2+ in the cytosol. Bifurcation analysis of the mathematical model showed that the loss of Ca2+ from the ER lumen decreased the sensitivity of cytosolic Ca2+ oscillations to IP3 [Ins(1,4,5)P3]. The addition of a high-affinity IP3R did not alter this property, but significantly decreased the sensitivity of the spike frequency to IP3. Our mathematical model demonstrates how luminal Ca2+, through its effect on Ca2+ uptake, can control cytosolic Ca2+ oscillations.
Substrate specificity of Helicobacter pylori histone-like HU protein is determined by insufficient stabilization of DNA flexure points
Authors: CHEN Christina , GHOSH Sharmistha , GROVE Anne 
Published: October 2004

The histone-like HU protein is ubiquitous in the eubacteria. A role for Escherichia coli HU in compaction of the bacterial genome has been reported, along with regulatory roles in DNA replication, transposition, repair and transcription. We show here that HU from the human pathogen Helicobacter pylori, which has been implicated in the development of ulcers and gastric cancer, exhibits enhanced thermal stability and distinct DNA substrate specificity. Thermal denaturation of HpyHU (H. pylori HU) measured by CD spectroscopy yields a melting temperature (Tm) of 56.4±0.1 °C. HpyHU binds linear duplex DNA with a site size of ∼19 bp and with low affinity, but in striking contrast to E. coli HU, HpyHU has only modest preference for DNA with mismatches, nicks or gaps. Instead, HpyHU binds stably to four-way DNA junctions with half-maximal saturation of 5 nM. Substitution of two residues adjacent to the DNA-intercalating prolines attenuates both the preference for flexible DNA and the ability to bend and supercoil DNA. These observations suggest that proline intercalation generates hinges that must be stabilized by adjacent residues; insufficient stabilization leads to reduced bending and a failure to bind preferably to DNA with flexure points, such as gaps and mismatches.
Optimal Design for Estimating Parameters of the 4-Parameter Hill Model
Authors: Khinkis Leonid A. , Levasseur Laurence , Faessel Hélène , Greco William R. 
Published: October 2004

Many drug concentration-effect relationships are described by nonlinear sigmoid models. The 4-parameter Hill model, which belongs to this class, is commonly used. An experimental design is essential to accurately estimate the parameters of the model. In this report we investigate properties of D-optimal designs. D-optimal designs minimize the volume of the confidence region for the parameter estimates or, equivalently, minimize the determinant of the variance-covariance matrix of the estimated parameters. It is assumed that the variance of the random error is proportional to some power of the response. To generate D-optimal designs one needs to assume the values of the parameters. Even when these preliminary guesses about the parameter values are appreciably different from the true values of the parameters, the D-optimal designs produce satisfactory results. This property of D-optimal designs is called robustness. It can be quantified by using D-efficiency. A five-point design consisting of four D-optimal points and an extra fifth point is introduced with the goals to increase robustness and to better characterize the middle part of the Hill curve. Four-point D-optimal designs are then compared to five-point designs and to log-spread designs, both theoretically and practically with laboratory experiments. D-optimal designs proved themselves to be practical and useful when the true underlying model is known, when good prior knowledge of parameters is available, and when experimental units are dear. The goal of this report is to give the practitioner a better understanding for D-optimal designs as a useful tool for the routine planning of laboratory experiments.
Nicotine enemas for treatment of ulcerative colitis: a study of the pharmacokinetics and adverse events associated with three doses of nicotine
Authors: Ingram J. R. , Routledge P. , Rhodes J. , Marshall R. W. , Buss D. C. , Evans B. K. , Feyerabend C. , Thomas G. A. O. 
Published: October 2004

SummaryBackground : Transdermal nicotine is of value in active ulcerative colitis but causes adverse events because of systemic absorption. Nicotine enemas may give rise to fewer adverse events.Aim : To assess the pharmacokinetics of nicotine enemas in three doses.Methods : Thirteen volunteers, all non‐smokers but three ex‐smokers, were given enemas on separate occasions containing 3, 6 and 9 mg of nicotine, in ascending dose order. Adverse events were recorded and blood samples taken over 8 h for measurement of serum nicotine and cotinine.Results : Enemas were retained by most subjects. Eleven of 14 adverse events were ‘early’– 30–105 min after the enema, corresponding to maximum plasma nicotine concentrations; three events were later, 4–8 h after the enema and unrelated to the tmax. ‘Early’ adverse events occurred in eight subjects – six with 9 mg. The three highest plasma nicotine concentrations were with 9 mg and associated with headache, nausea and sweating. Only one had adverse events with 3 mg and withdrew from the study. Nicotine Cmax with 6 and 9 mg doses were respectively two and three times the value with 3 mg. Peak nicotine concentrations occurred 44–50 min after the enema.Conclusion : The 6 mg dose of nicotine probably represents the dose to use in clinical practice – for the highest therapeutic dose with a low risk of adverse events.
Effect of xenon anaesthesia on accuracy of cardiac output measurement using partial CO2 rebreathing
Authors: Bein B. , Hanne P. , Hanss R. , Renner J. , Weber B. , Steinfath M. , Scholz J. , Tonner P. H. 
Published: October 2004

SummaryCardiac output (CO) determination based on partial CO2 rebreathing has recently been introduced into clinical practice. The determination of flow is crucial for exact CO readings and the physical properties of xenon, i.e. high density and viscosity, may influence flow readings. This study compared echocardiography‐derived CO measurements with the partial rebreathing method during total intravenous (TIVA) vs. xenon‐based anaesthesia. Thirty‐nine patients ASA physical status III undergoing aortic reconstruction were randomly assigned to receive either xenon (Xe, n = 20) or TIVA (T, n = 19) based general anaesthetic. Paired measurements were taken before xenon administration, after xenon administration, before and after clamping of the abdominal aorta and after declamping and at corresponding time points in the TIVA group. Data were analysed with a Bland‐Altmann plot. Bias and precision were acceptable and comparable before xenon administration (T 0.54 ± 0.92 l.min−1 vs. Xe 0.11 ± 1.1 l.min−1), but after xenon administration CO was largely overestimated by partial CO2 rebreathing (T 0.04 ± 0.91 l.min−1 vs. Xe −4.0 ± 2.1 l.min−1). In the TIVA group, bias and precision after declamping increased significantly (P < 0.01) compared to all time points except baseline. In its current application, the NICO cardiac output monitor appears to be inappropriate for determination of CO during xenon based anaesthesia.
von Willebrand disease: laboratory aspects of diagnosis and treatment
Authors: Favaloro E. J. , Lillicrap D. , Lazzari M. A. , Cattaneo M. , Mazurier C. , Woods A. , Meschengieser S. , Blanco A. , Kempfer A. C. , Hubbard A. , Chang A. 
Published: October 2004

Summary.
von Willebrand disease is the most common inherited bleeding disorder in humans. VWD can be classified into three major types, designated Types 1, 2 and 3; Type 2 can be further separated into subtypes 2A, 2B, 2M and 2N. The diagnosis of VWD requires a personal and family history of bleeding and confirmation by laboratory analysis. Although Types 2 and 3 are relatively straightforward to diagnose, there may be a risk of overdiagnosis of Type 1 because of an overlap within the normal range. We also report on the clinical profile and diagnosis of VWD in a South American cohort of patients and on the in vitro characteristics of some factor concentrates available for treatment of VWD.
Membrane isoforms of human immunoglobulins of the A1 and A2 isotypes: structural and functional study
Authors: LEDUC I. , DROUET M. , BODINIER M.‐C. , HELAL A. , COGNE M. 
Published: October 2004

SUMMARYAs for IgM, human IgA occurs either as soluble molecules in plasma and various other body fluids, or as membrane‐bound molecules on differentiated B cells, where they are part of the B‐cell receptor for antigen (BCR). We studied the structure of transcripts encoding the membrane‐anchored α‐chain of the human BCRα, which may be present in two different forms resulting from alternate splicing of the α‐chain mRNA (type I or type II). The ratio of type I versus type II did not vary upon stimulation of a B‐cell line with various cytokines. Rather, it differed strikingly in cells expressing either the IgA1 or IgA2 isotype of the BCRα, with virtually no type II α‐chain in the latter. Co‐modulation experiments also yielded different results for both isotypes, since they demonstrated a physical association of both membrane (m)IgA1 and mIgA2 with CD79b, the β component of the BCR Igα/Igβ heterodimer, but only of mIgA1 with CD19. Whatever the isotype, the BCR of the IgA class was able to carry out signal transduction upon cross‐linking by specific monoclonal antibodies but, in contrast to mIgM, it relied mainly on the entry of extracellular Ca2+ rather than on the release of intracellular stocks.