bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and characterization of ethoxy‐terminated ladder‐like polymethylsilsesquioxane oligomer
Authors: Duan Qinghua , Zhang Yong , Jiang Jinqiang , Deng Kuilin , Zhang Taoyi , Xie Ping , Zhang Rongben , Fu Pengfei 
Published: December 2003

AbstractA fully ethoxy‐terminated ladder‐like polymethylsilsesquioxane oligomer (EtO‐Me‐T) has been synthesized and characterized for the first time using an effective transient catalyst (tetramethylammonium hydroxide, TMAH) via the dehydration alcoholysis reaction of hydroxy‐terminated ladder‐like polymethylsilsesquioxane (HO‐Me‐T) prepared by a modified stepwise coupling polymerization approach. Compared with the common acidic or basic catalysts, use of the transient catalyst TMAH can not only make the HO‐Me‐T molecules fully ethoxy‐terminated but also enables the catalyst to be readily and thoroughly removed after completion of the alcoholysis reaction. It is noteworthy that the common acidic or basic catalysts widely used in the dehydration alcoholysis reaction are clearly unsuitable for the preparation of EtO‐Me‐T oligomer because the latter would be hydrolyzed unavoidably back to the parent HO‐Me‐T during the washing process. In addition, preliminary exploration indicates that, when compared with the tetraethyl orthosilicate (Si(OEt)4) generally used as a crosslinking agent for the room‐temperature vulcanization of silicone rubber (RTV‐SR), the oligomer EtO‐Me‐T is a promising replacement which can greatly improve the mechanical properties of RTV‐SR Copyright © 2003 Society of Chemical Industry
Solution structure of ADO1, a toxin extracted from the saliva of the assassin bug, Agriosphodrus dohrni
Authors: Bernard Cédric , Corzo Gerardo , Adachi‐Akahane Satomi , Foures Guillaume , Kanemaru Kazunori , Furukawa Yasuo , Nakajima Terumi , Darbon Hervé 
Published: December 2003

AbstractADO1 is a toxin purified from the saliva of the assassin bug, Agriosphodrus dohrni. Because of its similarity in sequence to Ptu1 from another assassin bug, we did not assess its pharmacologic target. Here, we demonstrate by electrophysiologic means that ADO1 targets the P/Q‐type voltage‐sensitive calcium channel. We also determine the solution structure of ADO1 using two‐dimensional NMR techniques, followed by distance geometry and molecular dynamics. The structure of ADO1 belongs to the inhibitory cystine knot (ICK) structural family (i.e., a compact disulfide‐bonded core from which four loops emerge). ADO1 contains a two‐stranded, antiparallel β‐sheet structure. We compare the structure of ADO1 with other voltage‐sensitive calcium‐channel blockers, analyze the topologic juxtaposition of key functional residues, and conclude that the recognition of voltage‐sensitive calcium channels by toxins belonging to the ICK structural family requires residues located on two distinct areas of the molecular surface of the toxins. Proteins 2003. © 2003 Wiley‐Liss, Inc.
Using evolutionary information for the query and target improves fold recognition
Authors: Wallner Björn , Fang Huisheng , Ohlson Tomas , Frey‐Skött Johannes , Elofsson Arne 
Published: December 2003

AbstractIn this study, we show that it is possible to increase the performance over PSI‐BLAST by using evolutionary information for both query and target sequences. This information can be used in three different ways: by sequence linking, profile–profile alignments, and by combining sequence–profile and profile–sequence searches. If only PSI‐BLAST is used, 16% of superfamily‐related protein domains can be detected at 90% specificity, but if a sequence–profile and a profile–sequence search are combined, this is increased to 20%, profile–profile searches detects 19%, whereas a linking procedure identifies 22% of these proteins. All three methods show equal performance, but the best combination of speed and accuracy seems to be obtained by the combined searches, because this method shows a good performance even at high specificity and the lowest computational cost. In addition, we show that the E‐values reported by all these methods, including PSI‐BLAST, underestimate the true rate of false positives. This behavior is seen even if a very strict E‐value cutoff and a limited number of iterations are used. However, the difference is more pronounced with a looser E‐value cutoff and more iterations. Proteins 2003;53:000–000. © 2003 Wiley‐Liss, Inc.
NH…O, OH…O, and CH…O hydrogen bonds in protein–ligand complexes: Strong and weak interactions in molecular recognition
Authors: Sarkhel Sanjay , Desiraju Gautam R. 
Published: December 2003

AbstractThe characteristics of NH…O, OH…O, and CH…O hydrogen bonds are examined in a group of 28 high‐resolution crystal structures of protein–ligand complexes from the Protein Data Bank and compared with interactions found in small‐molecule crystal structures from the Cambridge Structural Database. It is found that both strong and weak hydrogen bonds are involved in ligand binding. Because of the prevalence of multifurcation, the restrictive geometrical criteria set up for hydrogen bonds in small‐molecule crystal structures may need to be relaxed in macromolecular structures. For example, there are definite deviations from linearity for the hydrogen bonds in protein–ligand complexes. The formation of CH…O hydrogen bonds is influenced by the activation of the CαH atoms and by the flexibility of the side‐chain atoms. In contrast to small‐molecule structures, anticooperative geometries are common in the macromolecular structures studied here, and there is a gradual lengthening as the extent of furcation increases. CH…O bonds formed by Gly, Phe, and Tyr residues are noteworthy. The numbers of hydrogen bond donors and acceptors agree with Lipinski's “rule of five” that predicts drug‐like properties. Hydrogen bonds formed by water are also seen to be relevant in ligand binding. Ligand CH…Ow interactions are abundant when compared to NH…Ow and OH…Ow. This suggests that ligands prefer to use their stronger hydrogen bond capabilities for use with the protein residues, leaving the weaker interactions to bind with water. In summary, the interplay between strong and weak interactions in ligand binding possibly leads to a satisfactory enthalpy–entropy balance. The implications of these results to crystallographic refinement and molecular dynamics software are discussed. Proteins 2004. ©2003 Wiley‐Liss, Inc.
From “Try It and See” to strategic exploration: Characterizing young children's scientific reasoning
Authors: Tytler Russell , Peterson Suzanne 
Published: December 2003

AbstractThis article explores ways of characterizing different dimensions and levels of scientific reasoning in early elementary school children, in the context of open explorations. The article focuses on children's performance on three probes which involve using evidence to generate and evaluate knowledge claims. A number of dimensions have been used to characterize children's approaches to exploration and knowledge construction, which demonstrate the interrelationship between conceptual knowledge and scientific reasoning. Children differed markedly across these dimensions, yet individual children were relatively consistent in their approach to the tasks. The major differences in performance are linked to fundamental distinctions in the way ideas are viewed in relation to evidence. © 2003 Wiley Periodicals, Inc. J Res Sci Teach 41: 94–118, 2004
Linear Approximation of Execution-Time Constraints
Authors: Lermer Karl , Fidge Colin J. , Hayes Ian J. 
Published: December 2003

Abstract.
This paper defines an algorithm for predicting worst-case and best-case execution times, and determining execution-time constraints of control-flow paths through real-time programs using their partial correctness semantics. The algorithm produces a linear approximation of path traversal conditions, worst-case and best-case execution times and strongest postconditions for timed paths in abstract real-time programs. Also shown are techniques for determining the set of control-flow paths with decidable worst-case and best-case execution times. The approach is based on a weakest liberal precondition semantics and relies on supremum and infimum calculations similar to standard computations from linear programming and Presburger arithmetic. The methodology is applicable to any executable language with a predicate transformer semantics and hence provides a verification basis for both high-level language and assembly code execution-time analysis.
Neonatal screening for cystic fibrosis: France rises to the challenge
Authors: Farriaux J. P. , Vidailhet M. , Briard M. L. , Belot V. , Dhondt J. L. 
Published: December 2003

AbstractSummary: This paper describes the adjustments to the French neonatal screening programme required by the introduction of systematic screening for cystic fibrosis (CF), taking into account both the legal and statutory framework and the lessons of a pilot study carried out 10 years ago. The French association for the screening and prevention of infant handicaps (AFDPHE) has been mandated by its regulatory agencies to organize screening for CF in France (metropolitan and overseas territories). During the year 2001, expert groups (Technical Aspects, Information, Ethics and Genetics, Criteria for CF Centres, Protocol for the Care of a Newborn with CF) issued recommendations for the establishment of a national programme that would guarantee efficiency and adequate patient care from the time of diagnosis onward. The programme is based on a strategy combining immunoreactive trypsin (IRT) assay and the analysis of DNA mutations in dried blood samples obtained at 3 days of age. When an elevated IRT value is found, DNA analysis is performed on the same sample. Owing to the relative regional heterogeneity existing in France, 30 selected mutations are used, which provide 85% coverage. The Ethics and Genetics Committee recommended that, in order to avoid arousing anxiety by a recall, informed consent, according to the French legislation on bioethics, should be obtained for all neonates at birth by having the parents sign directly on the sampling paper. Information brochures for parents and health professionals have been designed. A new organization of patient care, involving the creation of CF centres recognized by the Ministry of Health, has been decided; all children diagnosed are to be referred to such centres, where they can be well cared for by a trained staff with sufficient means. The programme was implemented region by region in France, from the beginning of the year 2002 to early 2003. The expert groups still meet periodically to evaluate the implementation of the programme and to check that the terms of the agreement between the AFDPHE and the Social Security Agency are complied with.
Two novel mutations in the gene for human α‐mannosidase that cause α‐mannosidosis
Authors: Beccari T. , Bibi L. , Ricci R. , Antuzzi D. , Burgalossi A. , Costanzi E. , Orlacchio A. 
Published: December 2003

AbstractSummary: Mutation analysis performed on two Italian patients with α‐mannosidosis allowed the identification of two new mutations, IVS20−2A>G and 322–323insA. The patients were both homozygous for these mutations. The first mutation causes skipping of exon 21, whereas the second causes a frameshift introducing a stop codon at position 160 of the amino acid sequence.
Effect of cardiac vagal outflow on complexity and fractal correlation properties of heart rate dynamics
Authors: Penttilä J. , Helminen A. , Jartti T. , Kuusela T. , Huikuri H. V. , Tulppo M. P. , Scheinin H. 
Published: December 2003

Summary1 Cardiac vagal outflow is the major factor determining the magnitude of heart rate (HR) variability analysed by traditional time and frequency domain methods. New analysis techniques, such as fractal and complexity methods, have been developed to probe non‐linear features in HR behaviour that may not be detectable by traditional methods.2 We investigated the effects of vagal blockade (glycopyrrolate i.v. 5 μg kg−1 h−1 for 2 h, n = 8 vs. unmedicated control group, n = 8) and various breathing patterns (n = 12) on two non‐linear measures of HR variability – detrended fluctuation analysis (DFA) and approximate entropy (ApEn) – in healthy male volunteers.3 Glycopyrrolate decreased the mean (±SD) ApEn from 1.46 ± 0.18 to 0.85 ± 0.24 (P = 0.001 in comparison with the control group), and increased the short‐term (α1) and intermediate‐term (α2) fractal scaling exponents of DFA, α1 from 0.96 ± 0.19 to 1.43 ± 0.29 (P = 0.003) and α2 from 1.13 ± 0.10 to 1.34 ± 0.14 (P < 0.001).4 Decrease in fixed respiration rate from 15 to 6 breaths min−1 increased α1 from 0.83 ± 0.25 to 1.18 ± 0.27 (P < 0.001), but decreased α2 from 0.88 ± 0.09 to 0.45 ± 0.17 (P < 0.001) and ApEn from 1.26 ± 0.12 to 1.10 ± 0.14 (P = 0.028). Rapid breathing (24 min−1) had no influence on these non‐linear measures of HR variability. Hyperventilation (15 min−1, tidal volume increased voluntarily by 0.5 l) decreased α1 from 0.83 ± 0.25 to 0.66 ± 0.28 (P = 0.002) but did not affect α2 or ApEn.5 To conclude, vagal blockade alters the fractal scaling properties of R‐R intervals (α1, α2) and reduces the complexity (ApEn) of HR behaviour. Both the fractal and complexity measures of HR variability can also be influenced by changes in the breathing pattern.
Demonstration of functional receptors for noradrenaline and adenosine‐5′‐triphosphate, but not for prostaglandin E2, in HT‐29 human colon cancer cell line
Authors: Nylund G. , Nordgren S. , Delbro D. S. 
Published: December 2003

Summary1 The aim of the current study was to investigate in HT‐29 human colon cancer cell line, the existence of functional receptors for the signalling molecules, noradrenaline (NA), prostaglandin E2 (PGE2), and adenosine‐5′‐triphosphate (ATP).2 We utilized microphysiometry, which monitors on‐line extracellular acidification rate (ECAR) as a measure of cellular metabolic activity, and how this variable is altered by signalling molecules.3 Challenge with NA (5.9 μm) resulted in an increase in ECAR by approximately 24% of basal.4 PGE2 (0.0284, 0.284 and 2.84 μm) hardly affected ECAR.5 ATP (100 μm) elicited a biphasic effect on ECAR (increase and decrease in ECAR by about 58 and 10% of basal, respectively).6 HT‐29 cells were shown to express COX‐2 by immunocytochemistry.7 These data suggest the presence of functional receptors for NA and ATP, but not for PGE2 in HT‐29 human colon cancer cell line.
Identifying periodically expressed transcripts in microarray time series data
Authors: Wichert Sofia , Fokianos Konstantinos , Strimmer Korbinian 
Published: December 2003

Abstract
Motivation: Microarray experiments are now routinely used to collect large-scale time series data, for example to monitor gene expression during the cell cycle. Statistical analysis of this data poses many challenges, one being that it is hard to identify correctly the subset of genes with a clear periodic signature. This has lead to a controversial argument with regard to the suitability of both available methods and current microarray data.
Methods: We introduce two simple but efficient statistical methods for signal detection and gene selection in gene expression time series data. First, we suggest the average periodogram as an exploratory device for graphical assessment of the presence of periodic transcripts in the data. Second, we describe an exact statistical test to identify periodically expressed genes that allows one to distinguish periodic from purely random processes. This identification method is based on the so-called g-statistic and uses the false discovery rate approach to multiple testing.
Results: Using simulated data it is shown that the suggested method is capable of identifying cell-cycle-activated genes in a gene expression data set even if the number of the cyclic genes is very small and regardless the presence of a dominant non-periodic component in the data. Subsequently, we re-examine 12 large microarray time series data sets (in part controversially discussed) from yeast, human fibroblast, human HeLa and bacterial cells. Based on the statistical analysis it is found that a majority of these data sets contained little or no statistical significant evidence for genes with periodic variation linked to cell cycle regulation. On the other hand, for the remaining data the method extends the catalog of previously known cell-cycle-specific transcripts by identifying additional periodic genes not found by other methods. The problem of distinguishing periodicity due to generic cell cycle activity and to artifacts from synchronization is also discussed.
Availability: The approach has been implemented in the R package GeneTS available from http://www.stat.uni-muenchen.de/~strimmer/software.html under the terms of the GNU General Public License.
Prediction of protein subcellular locations using fuzzy k-NN method
Authors: Huang Ying , Li Yanda 
Published: December 2003

Abstract
Motivation: Protein localization data are a valuable information resource helpful in elucidating protein functions. It is highly desirable to predict a protein's subcellular locations automatically from its sequence.
Results: In this paper, fuzzy k-nearest neighbors (k-NN) algorithm has been introduced to predict proteins' subcellular locations from their dipeptide composition. The prediction is performed with a new data set derived from version 41.0 SWISS-PROT databank, the overall predictive accuracy about 80% has been achieved in a jackknife test. The result demonstrates the applicability of this relative simple method and possible improvement of prediction accuracy for the protein subcellular locations. We also applied this method to annotate six entirely sequenced proteomes, namely Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Oryza sativa, Arabidopsis thaliana and a subset of all human proteins.
Availability: Supplementary information and subcellular location annotations for eukaryotes are available at http://166.111.30.65/hying/fuzzy_loc.htm
Adaptive stochastic-deterministic chemical kinetic simulations
Authors: Vasudeva Karan , Bhalla Upinder S. 
Published: December 2003

Abstract
Motivation: Biochemical signaling pathways and genetic circuits often involve very small numbers of key signaling molecules. Computationally expensive stochastic methods are necessary to simulate such chemical situations. Single-molecule chemical events often co-exist with much larger numbers of signaling molecules where mass-action kinetics is a reasonable approximation. Here, we describe an adaptive stochastic method that dynamically chooses between deterministic and stochastic calculations depending on molecular count and propensity of forward reactions. The method is fixed timestep and has first order accuracy. We compare the efficiency of this method with exact stochastic methods.
Results: We have implemented an adaptive stochastic-deterministic approximate simulation method for chemical kinetics. With an error margin of 5%, the method solves typical biologically constrained reaction schemes more rapidly than exact stochastic methods for reaction volumes &gt;1–10 µm3. We have developed a test suite of reaction cases to test the accuracy of mixed simulation methods.
Availability: Simulation software used in the paper is freely available from http://www.ncbs.res.in/kinetikit/download.html
Supplementary information: A GENESIS/Kinetikit implementation of models and the test suite used in this paper are available from http://www.ncbs.res.in/kinetikit/download.html and also from the DOQCS database, http://doqcs.ncbs.res.in
HomGL—comparing genelists across species and with different accession numbers
Authors: Blüthgen Nils , Kiełbasa Szymon M. , Čajavec Branka , Herzel Hanspeter 
Published: December 2003

Abstract
Summary:Homology Gene List (HomGL) is a web-based tool for comparing gene lists with different accession numbers and identifiers and between different organisms. UniGene, LocusLink, HomoloGene and Ensembl databases are utilized to map between these lists and to retrieve upstream or transcribed sequences for genes in these lists. We illustrate the use of HomGL with respect to microarray studies and promoter analysis.
Availability: http://homgl.biologie.hu-berlin.de/
A generalized likelihood ratio test to identify differentially expressed genes from microarray data
Authors: Wang Song , Ethier Stewart 
Published: December 2003

Abstract
Motivation: Microarray technology emerges as a powerful tool in life science. One major application of microarray technology is to identify differentially expressed genes under various conditions. Currently, the statistical methods to analyze microarray data are generally unsatisfactory, mainly due to the lack of understanding of the distribution and error structure of microarray data.
Results: We develop a generalized likelihood ratio (GLR) test based on the two-component model proposed by Rocke and Durbin to identify differentially expressed genes from microarray data. Simulation studies show that the GLR test is more powerful than commonly used methods, like the fold-change method and the two-sample t-test. When applied to microarray data, the GLR test identifies more differentially expressed genes than the t-test, has a lower false discovery rate and shows more consistency over independently repeated experiments.
Availability: The approach is implemented in software called GLR, which is freely available for downloading at http://www.cc.utah.edu/~jw27c60
Essentiality and damage in metabolic networks
Authors: Lemke Ney , Herédia Fabiana , Barcellos Cláudia K. , dos Reis Adriana N. , Mombach José C. M. 
Published: December 2003

Abstract
Understanding the architecture of physiological functions from annotated genome sequences is a major task for postgenomic biology. From the annotated genome sequence of the microbe Escherichia coli, we propose a general quantitative definition of enzyme importance in a metabolic network. Using a graph analysis of its metabolism, we relate the extent of the topological damage generated in the metabolic network by the deletion of an enzyme to the experimentally determined viability of the organism in the absence of that enzyme. We show that the network is robust and that the extent of the damage relates to enzyme importance. We predict that a large fraction (91%) of enzymes causes little damage when removed, while a small group (9%) can cause serious damage. Experimental results confirm that this group contains the majority of essential enzymes. The results may reveal a universal property of metabolic networks.
PARIS: a proteomic analysis and resources indexation system
Authors: Wang Juhui , Caron Christophe , Mistou Michel-Yves , Gitton Christophe , Trubuil Alain 
Published: December 2003

Abstract
Summary: We developed a system for managing data from two-dimensional electrophoresis-based proteomic experiments. Named PARIS, the system stores gel image and information about experiments and analysis procedures, allows the user to search and navigate in genomic and proteomic data, supports visual verification and validation of the analysis results, and provides tools for cross multi-experiment and multi-experimenter data validation and exploration.
Availability: The software is freely available from http://www.inra.fr/bia/J/imaste/Projets/PARIS/index.html