bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypertrophic Cardiomyopathy: Low Frequency of Mutations in the β-Myosin Heavy Chain (MYH7) and Cardiac Troponin T (TNNT2) Genes among Spanish Patients
Authors: Garcı́a-Castro Mónica , Reguero Julián R , Batalla Alberto , Dı́az-Molina Beatriz , González Pelayo , Alvarez Victoria , Cortina Arturo , Cubero Gustavo I , Coto Eliecer
Published: February 2004

Background: Mutations in the cardiac β-myosin heavy chain (MYH7) and cardiac troponin T (TNNT2) genes are reportedly responsible for up to 40% of familial cases with hypertrophic cardiomyopathy (HC). Although there are no mutational hotspots, most of the mutations are located in specific exons of the MYH7 and TNNT2 genes. Currently it is not possible to predict the phenotype in carriers of mutations in these genes, although it is widely accepted that mutations in the MYH7 gene predispose to severe HC, whereas TNNT2 mutations are frequently linked to sudden cardiac death (SCD) in spite of minimal hypertrophy.

Methods: We sequenced exons 8, 9, 13–16, 19, 20, 22–24, and 30 of the MYH7 gene and exons 8, 9, 11, and 14–16 of the TNNT2 gene in 30 HC patients (18–60 years of age) from the region of Asturias (Northern Spain); 25 cases (80%) had a family history of the disease. Genomic DNA was amplified, and fragments were directly sequenced. Each DNA variant found in the patients was also analyzed in 200 healthy controls through single-strand conformation analysis.

Results: Four of the probands had nucleotide changes absent in the healthy controls. Two cases had mutations previously described in the MYH7 gene (exon 14, Arg453Cys) or the TNNT2 gene (exon 16, Arg278Cys). Two cases had new mutations (MYH7 exon 22, Met822Val; TNNT2 exon 14, Lys247Arg) not found among the healthy controls. We found MYH7 Met822Val in a woman with a severe form of HC; the mutation was absent in her parents, indicating a de novo mutation. MYH7 R453C was present in a woman with mild HC, mother of a son who died from SCD. TNNT2 R278C was present in a woman with severe HC, but a sister and a daughter were mutation carriers and did not have hypertrophy. A patient with severe HC was carrier of TNNT2 247Arg.

Conclusions:Mutations in the MYH7 and TNNT2 genes can be found in patients without a family history of HC. However, compared with other populations MYH7 or TNNT2 mutations were rare among our HC patients. This study illustrates the extreme phenotypic heterogeneity in carriers of MYH7 or TNNT2 mutations.
Quantification of Mitochondrial DNA Deletion, Depletion, and Overreplication: Application to Diagnosis
Authors: Chabi Béatrice , Mousson de Camaret Bénédicte , Duborjal Hervé , Issartel Jean-Paul , Stepien Georges
Published: February 2004

Background: Many mitochondrial pathologies are quantitative disorders related to tissue-specific deletion, depletion, or overreplication of mitochondrial DNA (mtDNA). We developed an assay for the determination of mtDNA copy number by real-time quantitative PCR for the molecular diagnosis of such alterations.

Methods: To determine altered mtDNA copy number in muscle from nine patients with single or multiple mtDNA deletions, we generated calibration curves from serial dilutions of cloned mtDNA probes specific to four different mitochondrial genes encoding either ribosomal (16S) or messenger (ND2, ND5, and ATPase6) RNAs, localized in different regions of the mtDNA sequence. This method was compared with quantification of radioactive signals from Southern-blot analysis. We also determined the mitochondrial-to-nuclear DNA ratio in muscle, liver, and cultured fibroblasts from a patient with mtDNA depletion and in liver from two patients with mtDNA overreplication.

Results: Both methods quantified 5–76% of deleted mtDNA in muscle, 59–97% of mtDNA depletion in the tissues, and 1.7- to 4.1-fold mtDNA overreplication in liver. The data obtained were concordant, with a linear correlation coefficient (r2) between the two methods of 0.94, and indicated that quantitative PCR has a higher sensitivity than Southern-blot analysis.

Conclusions: Real-time quantitative PCR can determine the copy number of either deleted or full-length mtDNA in patients with mitochondrial diseases and has advantages over classic Southern-blot analysis.
C-reactive Protein Concentration Distribution among US Children and Young Adults: Findings from the National Health and Nutrition Examination Survey, 1999–2000
Authors: Ford Earl S , Giles Wayne H , Myers Gary L , Rifai Nader , Ridker Paul M , Mannino David M
Published: February 2004

Background: The distribution of C-reactive protein (CRP) concentrations among children and young adults in the US is not known at present.

Methods: We used data from 3348 US children and young adults 3–19 years of age who participated in the National Health and Nutrition Examination Survey, 1999–2000, to describe the distribution of CRP concentrations, based on results obtained with a high-sensitivity latex-enhanced turbidimetric assay.

Results: The range of CRP concentrations was 0.1–90.8 mg/L (mean, 1.6 mg/L; geometric mean, 0.5 mg/L; median, 0.4 mg/L). CRP concentrations increased with age. Females 16–19 years of age had higher concentrations than males in this age range (P = 0.003). Mexican Americans had the highest CRP concentrations among the three major race or ethnic groups (P <0.001).

Conclusions: For the first time, these data describe the CRP concentration distribution among US children and young adults, based on results obtained with a high-sensitivity assay.
Profiling of Pentose Phosphate Pathway Intermediates in Blood Spots by Tandem Mass Spectrometry: Application to Transaldolase Deficiency
Authors: Huck Jojanneke H J , Struys Eduard A , Verhoeven Nanda M , Jakobs Cornelis , van der Knaap Marjo S
Published: February 2004

Background: Recently, several patients with abnormal polyol profiles in body fluids have been reported, but the origins of these polyols are unknown. We hypothesized that they are derived from sugar phosphate intermediates of the pentose phosphate pathway (PPP), and we developed a semiquantitative method for profiling of pentose phosphate pathway intermediates.

Methods: Sugar phosphates in blood spots were simultaneously analyzed by liquid chromatography–tandem mass spectrometry using an ion-pair-loaded C18 HPLC column. The tandem mass spectrometer was operated in the multiple-reaction monitoring mode. Enzymatically prepared d-[13C6]glucose 6-phosphate was used as internal standard. The method was used to study sugar phosphates abnormalities in a patient affected with a deficiency of transaldolase (TALDO1; EC 2.2.1.2).

Results: In control blood spots, dihydroxyacetone phosphate, pentulose 5-phosphates, pentose 5-phosphates, hexose 6-phosphates, and sedoheptulose 7-phosphate were detected. Detection limits ranged from ∼100 to ∼500 nmol/L. Glyceraldehyde 3-phosphate and erythrose 4-phosphate were undetectable. Intra- and interassay imprecision (CVs) were 10–17% and 12–21%, respectively. In blood from the TALDO1-deficient patient, sedoheptulose 7-phosphate was increased.

Conclusions: The new method allows investigation of patients in whom a defect in the PPP is suspected. Measurements of sugar phosphate intermediates of the PPP may provide new insights into metabolic defects underlying the accumulating polyols.
Sensitivity and Specificity of the Cozart Microplate EIA Cocaine Oral Fluid at Proposed Screening and Confirmation Cutoffs
Authors: Kim Insook , Barnes Allan J , Schepers Raf , Moolchan Eric T , Wilson Lisa , Cooper Gail , Reid Claire , Hand Chris , Huestis Marilyn A
Published: February 2004

Background: Oral fluid is currently being evaluated as an alternative matrix for monitoring illicit drugs in federally mandated workplace drug testing, for addiction treatment programs, and for driving under the influence testing. The sensitivity, specificity, and efficiency of the Cozart® Microplate EIA Cocaine Oral Fluid Kit (COC ELISA) were determined by comparison with gas chromatography–mass spectrometry (GC/MS) results at screening and confirmation cutoffs proposed in the US and UK.

Method: Oral fluid was collected by expectoration after citric acid candy stimulation or with Salivette® neutral cotton swabs or Salivette citric acid-treated cotton swabs before and after cocaine (COC) administration. Specimens (n = 1468) were analyzed with the COC ELISA for screening and with solid-phase extraction followed by GC/MS for confirmation. Three screening cutoffs (10, 20, and 30 μg/L) and four GC/MS cutoffs (2.5, 8, 10, and 15 μg/L COC, benzoylecgonine, and/or ecgonine methyl ester) were evaluated. GC/MS limit of quantification was 2.5 μg/L for all analytes.

Results: COC ELISA interassay imprecision (CV; n = 19) was 16% at 16.7 μg/L and 12% at 81.8 μg/L. With the 2.5, 8, 10, and 15 μg/L GC/MS cutoffs, 59.0%, 54.7%, 52.7%, and 48.7% of the oral fluid specimens were positive, respectively. Sensitivity, specificity, and efficiency were 92.2%, 84.7%, and 88.8%, respectively, for the suggested Substance Abuse and Mental Health Services Administration (SAMHSA) cutoffs and 90.2%, 89.2%, and 89.7% for cutoffs currently used in the UK.

Conclusions: COC ELISA had suitable sensitivity, specificity, and efficiency for identifying COC exposure at both the proposed SAMHSA and UK cutoffs. Sensitivity, specificity, and efficiency were >84% for both cutoffs, but 92 additional true-positive samples were identified with the SAMHSA cutoffs.
Fatigue‐Life Prediction of Magnesium Alloys for Structural Applications
Authors: Bin Sajuri Z. , Umehara T. , Miyashita Y. , Mutoh Y.
Published: February 2004

There has been growing interest in studies on fatigue strength and fatigue crack growth behavior of magnesium alloys. In the present study, fatigue‐life prediction of magnesium alloys based on a fracture mechanical approach has been made, where the pit depth for an extruded AZ61 at high humidity and the inherent defect diameter for a die‐cast AZ91D were assumed as an initial crack.
Microstructural Design for Enhanced Elevated Temperature Properties in Sand‐castable Magnesium Alloys
Authors: Bettles C.J. , Gibson M.A.
Published: February 2004

The low pressure and gravity casting processing techniques offer the component designer an opportunity to produce pieces with increased complexity over those able to be fabricated via the high pressure die casting route. The design of appropriate microstructures for the enhancement of elevated temperature properties is dependent on the chosen processing route, with the low pressure and gravity techniques allowing for post‐cast manipulation of the microstructure through heat treatment. There are competing microstructural requirements for strength and creep resistance in casting alloys, and the optimised microstructure must, of necessity, be a compromise. The contributions from solid solution strengthening, grain boundaries and precipitation processes are described, with particular reference to elevated temperature magnesium alloys.
Sagittal clefting of the body and other vertebral developmental errors in Canadian Inuit skeletons
Authors: Merbs Charles F.
Published: February 2004

The objective of this study was to determine the expression, distribution in the column, and overall frequency of sagittal clefting of the vertebral body in the skeletons of two Canadian Inuit groups. One group, referred to as Thule‐Historic, lived along the coast northwest of Hudson Bay, while the other, known as the Sadlermiut, were limited to Southampton Island and Coats Island north of Hudson Bay. The Thule‐Historic people are thought to be the ancestors of the present‐day Inuit of this region, whereas the much smaller, relatively isolated Sadlermiut became extinct during the winter of 1902–1903. The sagittal clefting results were also compared with those obtained for two other vertebral developmental problems, segmentation error and spina bifida. Sagittal clefting was found to occur with high frequency in the two Inuit series, especially in the region T6–T10. Segmentation errors were found to occur in approximately the same region of the column, while spina bifida produced a completely different pattern, occurring primarily at T11 and S1. The T11 involvement is limited to females, while S1 involvement occurs primarily in males. Sagittal clefting and spina bifida occur in the same individual more frequently than sagittal clefting and segmentation error. Possibly reflecting the smaller population size and isolated location of the Sadlermiut, sagittal clefting was found with greater frequency and intensity in the skeletons of this group than in those of the Thule‐Historic Inuit. Am J Phys Anthropol, 2003. © 2003 Wiley‐Liss, Inc.
Sedentism, seasonality, and economic status: A multivariate analysis of maternal dietary and health statuses between pastoral and agricultural Ariaal and Rendille communities in northern Kenya
Authors: Fujita Masako , Roth Eric Abella , Nathan Martha A. , Fratkin Elliot
Published: February 2004

This paper examines longitudinal data to assess the effects of the recent transition from pastoralism to sedentary agriculture for Ariaal and Rendille mothers in northern Kenya. Dietary, morbidity, and anthropometric data resulting from bimonthly repeated surveys of the pastoral community of Lewogoso and the sedentary agricultural community of Songa, covering the period from September 1994–July 1995, were used to test two hypotheses: 1) that sedentism is associated with changes in diet, seasonality, morbidity, and socioeconomic differentiation, and 2) that these changes affect maternal body composition. The first hypothesis is partly supported, with starch replacing milk in the sedentary diet. Repeated‐measures multivariate analysis of variance revealed no seasonal effects for diet in the agricultural sample, while starch consumption was significantly affected by seasonality for the pastoral sample. The agricultural community also featured economic dietary disparities favoring wealthier mothers, while no such effect was found in the pastoral community. However, no seasonal or economic effects were found for morbidity patterns in either sample. The second hypothesis is also partially supported, as a generalized estimating equations analysis revealed differences in the way diet and economic strata influence maternal anthropometric values. Economic status was significantly associated with maternal arm‐fat area in Lewogoso. Milk was a significant factor associated with maternal weight and arm‐muscle area in Songa. These findings are discussed in light of development policy implications. Am J Phys Anthropol, 2003. © 2003 Wiley‐Liss, Inc.
Hypothesis for the causes and periodicity of repetitive linear enamel hypoplasia in large, wild African (Pan troglodytes and Gorilla gorilla) and Asian (Pongo pygmaeus) apes
Authors: Skinner Mark F. , Hopwood David
Published: February 2004

Repetitive linear enamel hypoplasia (rLEH) is often observed in recent large‐bodied apes from Africa and Asia as well as Mid‐ to Late Miocene sites from Spain to China. The ubiquity and periodicity of rLEH are not understood. Its potential as an ontogenetic marker of developmental stress in threatened species (as well as their ancient relatives) makes rLEH an important if enigmatic problem. We report research designed to show the periodicity of rLEH among West African Pan troglodytes (12 male, 32 female), Gorilla gorilla (10 male, 10 female), and Bornean and Sumatran Pongo pygmaeus (11 male, 9 female, 9 unknown) from collections in Europe. Two methods were employed. In the common chimpanzees and gorillas, the space between adjacent, macroscopically visible LEH grooves on teeth with two or more episodes was expressed as an absolute measure and as a ratio of complete unworn crown height. In the orangutans, the number of perikymata between episode onsets, as well as duration of rLEH, was determined from scanning electron micrographs of casts of incisors and canines. We conclude that stress in the form of LEH commences as early as 2.5 years of age in all taxa and lasts for several years, and even longer in orangutans; the stress is not chronic but episodic; the stressor has a strong tendency to occur in pulses of two occurrences each; and large apes from both land masses exhibit rLEH with an average periodicity of 6 months (or multiples thereof; Sumatran orangutans seem to show only annual stress), but this needs further research. This is supported by evidence of spacing between rLEH as well as perikymata counts. Duration of stress in orangutans averages about 6 weeks. Finally, the semiannual stressor transcends geographic and temporal boundaries, and is attributed to regular moisture cycles associated with the intertropical convergence zone modified by the monsoon. While seasonal cycles can influence both disease and nutritional stress, it is likely the combination of seasonal variation in fruiting cycles with specific stressors (malaria and/or intestinal parasites, especially hookworm) that results in this widespread phenomenon. This seasonal stress is sufficiently common and of long duration (6 weeks on average in orangutans) that we think rLEH may reflect significant stress in recent and, inferentially, fossil apes. Increasing seasonality may have impinged negatively on later Miocene apes, especially if they lacked a clear birth peak or seasonality in their reproductive cycles. Am J Phys Anthropol, 2003. © 2003 Wiley‐Liss, Inc.
Ontogenetic correlates of diet in Malagasy lemurs
Authors: Godfrey L.R. , Samonds K.E. , Jungers W.L. , Sutherland M.R. , Irwin M.T.
Published: February 2004

There is a well‐documented relationship between development and other life‐history parameters among anthropoid primates. Smaller‐bodied anthropoids tend to mature more rapidly than do larger‐bodied species. Among anthropoids of similar body sizes, folivorous species tend to grow and mature more quickly than do frugivorous species, thus attaining adult body size at an earlier age. This pattern conforms to the expectations of Janson and van Schaik's “ecological risk aversion hypothesis,” which predicts that rates of growth and maturation should vary in inverse relation to the intensity of intraspecific feeding competition. According to the ecological risk aversion hypothesis (RAH), species experiencing high intraspecific feeding competition will grow and mature slowly to reduce the risk of mortality due to food shortages. Species experiencing low levels of intraspecific feeding competition will shorten the juvenile period to reduce the overall duration of this high‐risk portion of the life cycle. This paper focuses on development and maturation in lemurs. We show that folivorous lemurs (such as indriids) grow and mature more slowly than like‐sized frugivorous lemurs (e.g., most lemurids), but tend to exhibit faster dental development. Their dental developmental schedules are accelerated on an absolute scale, relative to craniofacial growth, and relative to particular life‐history landmarks, such as weaning. Dental development has a strong phylogenetic component: even those lemurids that consume substantial amounts of foliage have slower dental development than those indriids that consume substantial amounts of fruit. Implications of these results for the RAH are discussed, and an explanation for this hypothesis' failure to predict lemur growth schedules is offered. We propose that the differing developmental schedules of folivorous and frugivorous lemurs may reflect different solutions to the ecological problem of environmental instability: some rely on a strategy of low maternal input and slow returns, while others rely on a strategy of high maternal input and fast returns. Am J Phys Anthropol, 2003. © 2003 Wiley‐Liss, Inc.
Analysis and significance of linear enamel hypoplasia in Plio‐Pleistocene hominins
Authors: Guatelli‐Steinberg Debbie
Published: February 2004

This study of linear enamel hypoplasia (LEH) in Plio‐Pleistocene hominins builds on a previous study (Guatelli‐Steinberg [2003] Am. J. Phys. Anthropol. 120:309–322) that focused on LEH in early South African hominins. The present study is more comprehensive, encompassing dental specimens of hominins from East Africa as well, including early Homo. As a developmental defect of enamel, LEH is used in anthropological contexts to reveal information about physiological stress. However, intrinsic aspects of enamel development and morphology can affect the expression of LEH, complicating efforts to understand the significance of these defects. In this study, the analysis of LEH is conducted with respect to enamel development and morphology. It is predicted that Paranthropus should have fewer defects on its canine teeth than Australopithecus and Homo, owing to its abbreviated period of enamel formation. This prediction is supported: Paranthropus has statistically significantly fewer defects per canine than Australopithecus and Homo. The previous study demonstrated that despite the wider spacing of perikymata on the teeth of South African Paranthropus, defects on the canine teeth of this genus were not wider than those of Australopithecus. A multiple linear regression analysis in that study, as well as a separate analysis in the present study, indicate that the number of perikymata within defects is a better predictor of defect width than perikymata spacing. In this study, it was additionally found that the average number of perikymata within Australopithecus defects is statistically significantly greater than it is in Paranthropus, thus explaining why Paranthropus defects are not wider than those of Australopithecus. The biological significance of this difference in the number of perikymata within the defects of Australopithecus and Paranthropus is considered in light of several factors, including: 1) the possibility that other intrinsic attributes of enamel morphology may be involved (specifically the faster extension rates of Paranthropus that result in shallower defects), 2) generic differences in the canalization of enamel development, and 3) generic differences in the duration of disruptions to enamel growth. Am J Phys Anthropol, 2003. © 2003 Wiley‐Liss, Inc.
Trends and issues in establishing interoperability among knowledge organization systems
Authors: Lei Zeng Marcia , Mai Chan Lois
Published: February 2004

This report analyzes the methodologies used in establishing interoperability among knowledge organization systems (KOS) such as controlled vocabularies and classification schemes that present the organized interpretation of knowledge structures. The development and trends of KOS are discussed with reference to the online era and the Internet era. Selected current projects and activities addressing KOS interoperability issues are reviewed in terms of the languages and structures involved. The methodological analysis encompasses both conventional and new methods that have proven to be widely accepted, including derivation/modeling, translation/adaptation, satellite and leaf node linking, direct mapping, co‐occurrence mapping, switching, linking through a temporary union list, and linking through a thesaurus server protocol. Methods used in link storage and management, as well as common issues regarding mapping and methodological options, are also presented. It is concluded that interoperability of KOS is an unavoidable issue and process in today's networked environment. There have been and will be many multilingual products and services, with many involving various structured systems. Results from recent efforts are encouraging.
Characterization of the impact of sets of scientific papers: The Garfield (impact) factor
Authors: Vinkler Peter
Published: February 2004

The Garfield (Impact) Factor (GF) is one of the most frequently used scientometric indicators. In the present article it is shown that the main factors determining the value of the mean GF representing a set of journals are the number of articles published recently (articles referencing) related to those published in a previous time period (articles to be referenced) and the mean number of references in journal papers referring to the time period selected. It has been proved further that GF corresponds to the mean chance for citedness of journal papers. A new indicator, Specific Impact Contribution (SIC), is introduced, which characterizes the contribution of a subset of articles or a journal to the total impact of the respective articles or journals. The SIC index relates the share of a journal in citations divided by that in publications within a set of papers or journals appropriately selected. It is shown, however, that the normalized GFs of journals and the normalized SIC indicators are identical measures within any set of journals selected. It may be stated therefore that Garfield Factors of journals (calculated correctly) are appropriate scientometric measures for characterizing the relative international eminence of journals within a set of journals appropriately selected. It is demonstrated further that SIC indicators (and so GF indexes) correspond to the (number of citations per paper) indicators generally used, within the same set of papers.
A survey of nucleotide cyclases in Actinobacteria: unique domain organization and expansion of the class III cyclase family in Mycobacterium tuberculosis
Authors: Shenoy Avinash R. , Sivakumar K. , Krupa A. , Srinivasan N. , Visweswariah Sandhya S.
Published: February 2004

Cyclic nucleotides are well‐known second messengers involved in the regulation of important metabolic pathways or virulence factors. There are six different classes of nucleotide cyclases that can accomplish the task of generating cAMP, and four of these are restricted to the prokaryotes. The role of cAMP has been implicated in the virulence and regulation of secondary metabolites in the phylum Actinobacteria, which contains important pathogens, such as Mycobacterium tuberculosis, M. leprae, M. bovis and Corynebacterium, and industrial organisms from the genus Streptomyces. We have analysed the actinobacterial genome sequences found in current databases for the presence of different classes of nucleotide cyclases, and find that only class III cyclases are present in these organisms. Importantly, prominent members such as M. tuberculosis and M. leprae have 17 and 4 class III cyclases, respectively, encoded in their genomes, some of which display interesting domain fusions seen for the first time. In addition, a pseudogene corresponding to a cyclase from M. avium has been identified as the only cyclase pseudogene in M. tuberculosis and M. bovis. The Corynebacterium and Streptomyces genomes encode only a single adenylyl cyclase each, both of which have corresponding orthologues in M. tuberculosis. A clustering of the cyclase domains in Actinobacteria reveals the presence of typical eukaryote‐like, fungi‐like and other bacteria‐like class III cyclase sequences within this phylum, suggesting that these proteins may have significant roles to play in this important group of organisms. Copyright © 2004 John Wiley & Sons, Ltd.
Identification and analysis of novel tandem repeats in the cell surface proteins of archaeal and bacterial genomes using computational tools
Authors: Adindla S. , Inampudi K. K. , Guruprasad K. , Guruprasad L.
Published: February 2004

We have identified four novel repeats and two domains in cell surface proteins encoded by the Methanosarcina acetivorans genome and in some archaeal and bacterial genomes. The repeats correspond to a certain number of amino acid residues present in tandem in a protein sequence and each repeat is characterized by conserved sequence motifs. These correspond to: (a) a 42 amino acid (aa) residue RIVW repeat; (b) a 45 aa residue LGxL repeat; (c) a 42 aa residue LVIVD repeat; and (d) a 54 aa residue LGFP repeat. The domains correspond to a certain number of aa residues in a protein sequence that do not comprise internal repeats. These correspond to: (a) a 200 aa residue DNRLRE domain; and (b) a 70 aa residue PEGA domain. We discuss the occurrence of these repeats and domains in the different proteins and genomes analysed in this work. Copyright © 2004 John Wiley & Sons, Ltd.
UTOPIA—user‐friendly tools for operating informatics applications
Authors: Pettifer S. R. , Sinnott J. R. , Attwood T. K.
Published: February 2004

Bioinformaticians routinely analyse vast amounts of information held both in large remote databases and in flat data files hosted on local machines. The contemporary toolkit available for this purpose consists of an ad hoc collection of data manipulation tools, scripting languages and visualization systems; these must often be combined in complex and bespoke ways, the result frequently being an unwieldy artefact capable of one specific task, which cannot easily be exploited or extended by other practitioners. Owing to the sizes of current databases and the scale of the analyses necessary, routine bioinformatics tasks are often automated, but many still require the unique experience and intuition of human researchers: this requires tools that support real‐time interaction with complex datasets. Many existing tools have poor user interfaces and limited real‐time performance when applied to realistically large datasets; much of the user's cognitive capacity is therefore focused on controlling the tool rather than on performing the research. The UTOPIA project is addressing some of these issues by building reusable software components that can be combined to make useful applications in the field of bioinformatics. Expertise in the fields of human computer interaction, high‐performance rendering, and distributed systems is being guided by bioinformaticians and end‐user biologists to create a toolkit that is both architecturally sound from a computing point of view, and directly addresses end‐user and application‐developer requirements. Copyright © 2004 John Wiley & Sons, Ltd.
A formal language‐based approach in biology
Authors: Gheorghe Marian , Mitrana Victor
Published: February 2004

This paper presents an overview of computational biology approaches and surveys some of the natural computing models using, in both cases, a formal language‐based approach. Copyright © 2004 John Wiley & Sons, Ltd.
The evolution of protein interaction networks in regulatory proteins
Authors: Amoutzias Gregory D. , Robertson David L. , Bornberg‐Bauer Erich
Published: February 2004

Interactions between proteins are essential for intracellular communication. They form complex networks which have become an important source for functional analysis of proteins. Combining phylogenies with network analysis, we investigate the evolutionary history of interaction networks from the bHLH, NR and bZIP transcription‐factor families. The bHLH and NR networks show a hub‐like structure with varying γ values. Mutation and gene duplication play an important role in adding and removing interactions. We conclude that in several of the protein families that we have studied, networks have primarily arisen by the development of heterodimerizing transcription factors, from an ancestral gene which interacts with any of the newly emerging proteins but also homodimerizes. Copyright © 2004 John Wiley & Sons, Ltd.
Signal analysis on strings for immune‐type pattern recognition
Authors: Atreas Nikolaos D. , Karanikas Costas , Polychronidou Persefoni
Published: February 2004

We use wavelet‐type discrete transforms for signal analysis on strings of finite length. We apply these transforms for edge and hidden Markov process detection. We also present new approaches for string matching and for measures of the diversity of chaotic strings. Copyright © 2004 John Wiley & Sons, Ltd.
Individual‐based modelling of bacterial ecologies and evolution
Authors: Vlachos C. , Gregory R. , Paton R. C. , Saunders J. R. , Wu Q. H.
Published: February 2004

This paper presents two approaches to the individual‐based modelling of bacterial ecologies and evolution using computational tools. The first approach is a fine‐grained model that is based on networks of interactivity between computational objects representing genes and proteins. The second approach is a coarser‐grained, agent‐based model, which is designed to explore the evolvability of adaptive behavioural strategies in artificial bacteria represented by learning classifier systems. The structure and implementation of these computational models is discussed, and some results from simulation experiments are presented. Finally, the potential applications of the proposed models to the solution of real‐world computational problems, and their use in improving our understanding of the mechanisms of evolution, are briefly outlined. Copyright © 2004 John Wiley & Sons, Ltd.
ArraySolver: an algorithm for colour‐coded graphical display and Wilcoxon signed‐rank statistics for comparing microarray gene expression data
Authors: Khan Haseeb Ahmad
Published: February 2004

The massive surge in the production of microarray data poses a great challenge for proper analysis and interpretation. In recent years numerous computational tools have been developed to extract meaningful interpretation of microarray gene expression data. However, a convenient tool for two‐groups comparison of microarray data is still lacking and users have to rely on commercial statistical packages that might be costly and require special skills, in addition to extra time and effort for transferring data from one platform to other. Various statistical methods, including the t‐test, analysis of variance, Pearson test and Mann–Whitney U test, have been reported for comparing microarray data, whereas the utilization of the Wilcoxon signed‐rank test, which is an appropriate test for two‐groups comparison of gene expression data, has largely been neglected in microarray studies. The aim of this investigation was to build an integrated tool, ArraySolver, for colour‐coded graphical display and comparison of gene expression data using the Wilcoxon signed‐rank test. The results of software validation showed similar outputs with ArraySolver and SPSS for large datasets. Whereas the former program appeared to be more accurate for 25 or fewer pairs (n ≤ 25), suggesting its potential application in analysing molecular signatures that usually contain small numbers of genes. The main advantages of ArraySolver are easy data selection, convenient report format, accurate statistics and the familiar Excel platform. Copyright © 2004 John Wiley & Sons, Ltd.
ProbSeq—a fragmentation model for interpretation of electrospray tandem mass spectrometry data
Authors: Skilling John , Denny Richard , Richardson Keith , Young Phillip , McKenna Thérèse , Campuzano Iain , Ritchie Mark
Published: February 2004

We describe a probabilistic peptide fragmentation model for use in protein databank searching and de novo sequencing of electrospray tandem mass spectrometry data. A probabilistic framework for tuning of the model using a range of well‐characterized samples are introduced. We present preliminary results of our tuning efforts. Copyright © 2004 John Wiley & Sons, Ltd.
Enabling proteomics: the need for an extendable ‘workbench’ for user‐configurable solutions
Authors: Beynon Robert J.
Published: February 2004

Proteomics has the capability to generate overwhelming quantities of data in relatively short timescales, and it is not uncommon to see experimenters investing substantially more time in data analysis than in data gathering. Although several sophisticated tools for data reduction and analysis are available, they lack the flexibility to cope with increasingly innovative experimental strategies and new database resources that encode both qualitative and quantitative data. I will outline a specification of a flexible proteomics tool that could address many current bottlenecks and deficiencies. Copyright © 2004 John Wiley & Sons, Ltd.
Synthetic Applications in Radical/Radical Cationic Cascade Reactions
Authors: Rinderhagen Heiko , Mattay Jochen
Published: February 2004

Oxidative photoinduced electron transfer (PET) reactions have been performed with various cyclic cyclopropyl(vinyl) silyl ethers bearing an olefinic or acetylenic side chain. The reactions result in bi‐ to tetracyclic ring systems via a fragmentation–radical/radical cationic addition reaction pathway with well defined ring juncture. The mode of cyclisation (endo/exo) can be partially controlled by addition of nucleophiles due to the suppression of radical cationic reaction pathways. Quantum chemical calculation of the cyclisation transition states underline the experimentally found selectivities. Additional mechanistic studies concerning the saturation step reveal that the final radical is saturated mostly by the solvent and traces of water in the solvent.
Nanostructured Pure γ‐Fe2O3 via Forced Precipitation in an Organic Solvent
Authors: Khaleel Abbas A.
Published: February 2004

Pure maghemite, γ‐Fe2O3, was prepared as ultra fine particles in the nanometer‐sized range via the forced precipitation method in an organic solvent. The precipitation of iron(III) ions, from iron(III) chloride in 2‐propanol led selectively to highly dispersed particles of ferrihydrite, which upon treatment with temperatures higher than 200 °C under dynamic vacuum resulted in high‐surface‐area particles of γ‐Fe2O3. Precipitation in water also led to ferrihydrite, but the final product, after heating at 300 °C, contained a mixture of γ‐Fe2O3 and α‐Fe2O3 (hematite). The precipitation from iron(III) nitrate in water resulted in goethite which was converted to hematite upon heating. On the other hand, the final product in 2‐propanol was a mixture of maghemite and hematite. The products were characterized by FTIR, TGA, XRD, and gas sorption analysis. Nitrogen gas adsorption studies for the pure γ‐Fe2O3 samples revealed mesoporous particles with high surface areas in the range of 70–120 m2 g−1 after heat treatment at 300 °C. The γ‐Fe2O3 particles retained their γ‐phase as well as their mesoporous structure at relatively high temperatures, as high as 400 °C.
Ring Currents as Probes of the Aromaticity of Inorganic Monocycles : P5−, As5−, S2N2, S3N3−, S4N3+, S4N42+, S5N5+, S42+ and Se42+
Authors: De Proft Frank , Fowler Patrick W. , Havenith Remco W. A. , Schleyer Paul von Ragué , Van Lier Gregory , Geerlings Paul
Published: February 2004

Current‐density maps were calculated by the ipsocentric CTOCD‐DZ/6‐311G** (CTOCD‐DZ=continuous transformation of origin of current density‐diamagnetic zero) approach for three sets of inorganic monocycles: S42+, Se42+, S2N2, P5− and As5− with 6 π electrons; S3N3−, S4N3+ and S4N42+ with 10 π electrons; and S5N5+ with 14 π electrons. Ipsocentric orbital analysis was used to partition the currents into contributions from small groups of active electrons and to interpret the contributions in terms of symmetry‐ and energy‐based selection rules. All nine systems were found to support diatropic π currents, reinforced by σ circulations in P5−, As5−, S3N3−, S4N3+, S4N42+ and S5N5+, but opposed by them in S42+, Se42+ and S2N2. The opposition of π and σ effects in the four‐membered rings is compatible with height profiles of calculated NICS (nucleus‐independent chemical shifts).
Perturbation of the NH2 pKa Value of Adenine in Platinum(II) Complexes: Distinct Stereochemical Internucleobase Effects
Authors: Garijo Añorbe Marta , Lüth Marc Sven , Roitzsch Michael , Morell Cerdà Marta , Lax Patrick , Kampf Gunnar , Sigel Helmut , Lippert Bernhard
Published: February 2004

The degree of acidification of the exocyclic N6 amino group of the model nucleobase 9‐methyladenine (9MeA) in relation to the number and site(s) of PtII binding has been studied in detail. It is found that twofold PtII binding to N1 and N7 lowers the pKa value from 16.7 in the free base to 12–8. The lowest pKa values are observed when the resulting N6H− amide group is intramolecularly stabilized by an H‐bond donor such as the N6H2 group of a suitably positioned second 9MeA ligand. Deprotonation of the N6 amino group facilitates Pt migration from N1 to N6, and subsequent reprotonation of the N1 position yields a twofold N7,N6‐metalated form of the rare imino tautomer of 9MeA, which has a pKa value of 5.03. These findings demonstrate a principle that is of potential relevance to the topic of “shifted pKa” values of adenine nucleobases, which is believed to be important with regard to acid–base catalysis of RNAs at physiological pH values. The principle states that a nucleobase pKa value can be sufficiently lowered to reach near‐neutral values and that the pKa value of the protonated base does not necessarily have to be increased to accomplish this effect.
Supramolecular Self‐Assembly of Conjugated Diblock Copolymers
Authors: Wang Hengbin , You Wei , Jiang Ping , Yu Luping , Wang H. Hau
Published: February 2004

This paper describes the synthesis and characterization of a novel series of copolymers with different lengths of oligo(phenylene vinylene) (OPV) as the rod block, and poly(propylene oxide) as the coil block. Detailed characterization by means of transmission electron microscopy (TEM), atomic force microscopy (AFM), and small‐angle neutron scattering (SANS) revealed the strong tendency of these copolymers to self‐assemble into cylindrical micelles in solution and as‐casted films on a nanometer scale. These micelles have a cylindrical OPV core surrounded by a poly(propylene glycol) (PPG) corona and readily align with each other to form parallel packed structures when mica is used as the substrate. A packing model has been proposed for these cylindrical micelles.
Three‐Phase Microemulsion/Sol–Gel System for Aqueous Catalysis with Hydrophobic Chemicals
Authors: Abu‐Reziq Raed , Blum Jochanan , Avnir David
Published: February 2004

A facile three‐phase transport process is described that allows to carry out catalytic reactions in water, whereby all components are hydrophobic. According to this process a hydrophobic substrate is microemulsified in water and subjected to an organometallic catalyst, which is entrapped within a partially hydrophobized sol–gel matrix. The surfactant molecules, which carry the hydrophobic substrate, adsorb/desorb reversibly on the surface of the sol–gel matrix breaking the micellar structure, spilling their substrate load into the porous medium that contains the catalyst. A catalytic reaction then takes place within the ceramic material to form the desired products that are extracted by the desorbing surfactant, carrying the emulsified product back into the solution. The method is general and versatile and has been demonstrated with the catalytic hydrogenations of alkenes, alkynes, aromatic CC bonds, and nitro and cyano groups.
Kinetics and Mechanisms for the Reactions of Phenyl Radical with Ketene and its Deuterated Isotopomer: An Experimental and Theoretical Study
Authors: Choi Y. M. , Lin M. C.
Published: February 2004

Kinetics and mechanism for the reaction of phenyl radical (C6H5) with ketene (H2CβCαO) were studied by the cavity ring‐down spectrometric (CRDS) technique and hybrid DFT and ab initio molecular orbital calculations. The C6H5 transition at 504.8 nm was used to detect the consumption of the phenyl radical in the reaction. The absolute overall rate constants measured, including those for the reaction with CD2CO, can be expressed by the Arrhenius equation k=(5.9±1.8)×1011 exp[−(1160±100)/T] cm3 mol−1 s−1 over a temperature range of 301–474 K. The absence of a kinetic isotope effect suggests that direct hydrogen abstraction forming benzene and ketenyl radical is kinetically less favorable, in good agreement with the results of quantum chemical calculations at the G2MS//B3LYP6‐31G(d) level of theory for all accessible product channels, including the above abstraction and additions to the Cα, Cβ, and O sites. For application to combustion, the rate constants were extrapolated over the temperature range of 298–2500 K under atmospheric pressure by using the predicted transition‐state parameters and the adjusted entrance reaction barriers Eα=Eβ=1.2 kcal mol−1; they can be represented by the following expression in units of cm3 mol−1 s−1: kα=6.2×1019 T−2.3 exp[−7590/T] and kβ=3.2×104 T2.4 exp[−246/T].
Two‐ and Three‐Dimensional Molecular Organization of Schiff‐Base Derivatives
Authors: Mu Zhong‐Cheng , Kong Jian‐Fei , Wang Yue , Ye Ling , Yang Guang‐Di , Zhang Xi
Published: February 2004

We have designed and synthesized a series of Schiff base derivatives, and studied their structural features in two‐dimensional (2D) and three‐dimensional (3D) states by combining scanning tunneling microscopy (STM) and X‐ray diffraction experiments. The Schiff‐base derivatives with short alkyl chains crystallize easily, which allows a detailed structural analysis by X‐ray diffraction. Due to the strong adsorbate–substrate interactions, those bases with long alkyl chains easily form 2D assemblies on highly oriented pyrolytic graphite (HOPG). The STM images indicate also that the introduction of two methoxy groups into the molecule can change the structure of these 2D assemblies as a result of the increased steric hindrances, for example: the Schiff‐base derivative, bearing both methoxy groups and C16H33 tails, forms 2D Moiré patterns, and an alignment of pairing Schiff‐base molecules may be easily resolved. Conversely, the Schiff base derivative, bearing solely C16H33 tails, forms 2D non‐Moiré patterns. It is demonstrated that the 3D structural features result from the compromise of intermolecular interactions of different molecular moieties. However, there is one more factor, which also governs the 2D structure: the adsorbate‐substrate interaction. The 3D crystal structure may thus help to understand many factors involved in the formation of 2D structures, and would be helpful for designing new molecular assemblies with tailoring functions.
Functional Microdomains of Glycolipids with Partially Fluorinated Membrane Anchors: Impact on Cell Adhesion
Authors: Gege Christian , Schneider Matthias F. , Schumacher Gabriele , Limozin Laurent , Rothe Ulrich , Bendas Gerd , Tanaka Motomu , Schmidt Richard R.
Published: February 2004

Functional microdomains of glycolipids were designed by mixing neoglycolipids with partially fluorinated alkyl (F‐alkyl) chains and matrix lipids with alkyl chains. Fluorescence images of the mixed lipid monolayers at the air–water interface demonstrated that it is possible to control both size and distribution of the microdomains by means of the strong demixing of alkyl and F‐alkyl membrane anchors, while the carbohydrate head groups seemed to play a rather minor role. These microdomains in monolayers could be transferred onto hydrophobized substrates and subjected to experiments in a dynamic flow chamber. The results obtained here clearly indicated that the dynamic adhesion of Chinese hamster ovarial cells expressing E‐selectin (CHO‐E cells) on a lipid monolayer containing microdomains of sialyl LewisX (sLeX) can be both enhanced and reduced by controlled demixing of ligands and matrices. Moreover, the same clusters of sLeX could also be formed in giant lipid vesicles, which can be used as a model cell that locally expresses biospecific functions.
Cover Picture: Functional Microdomains of Glycolipids with Partially Fluorinated Membrane Anchors: Impact on Cell Adhesion (ChemPhysChem 2/2004)
Authors: Gege Christian , Schneider Matthias F. , Schumacher Gabriele , Limozin Laurent , Rothe Ulrich , Bendas Gerd , Tanaka Motomu , Schmidt Richard R.
Published: February 2004

The cover picture shows a confocal microscopy image of glycolipid microdomains designed by mixing neoglycolipids with partially fluorinated (F‐alkyl) chains. For more information, see the Article by Tanaka et al. on pp. 216–224.
Nano‐fabrication of azopolymer by scanning near‐field optical microscope
Authors: Mori Wataru , Tawata Masahiro , Shimoyama Hiroshi , Ikawa Taiji , Tsuchimori Masaaki , Watanabe Osamu
Published: February 2004

Deformation of an organic photosensitive azopolymer by near‐field light generated by an optical fiber probe with a very small aperture diameter of about 50 nm is studied. The azopolymer is deformed in response to the polarization state of the light incident on the probe. If the probe aperture diameter is made smaller, the mark shape can be made smaller but the probe must be moved closer to the material. However, the mark width is about 6 times the probe aperture diameter. © 2004 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 87(3): 55–61, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10129