bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling Toxicity using Molecular Quantum Similarity Measures
Authors: Gironés Xavier , Carbó‐Dorca Ramon 
Published: April 2006

AbstractIn this work, a general procedure for the application of Molecular Quantum Similarity Measures (MQSM) into the Quantitative Structure‐Toxicity Relationships (QSTR) field is presented. The methodology is presented from its theoretical background, beginning with the formulation of MQSM and the role of density functions. Other topics, like molecular modelling, electronic density fitting, similarity scaling and molecular superposition are also analysed. The theoretical part is complemented with three different application examples dealing with acute aquatic toxicity related to different fish species. The molecular sets are constituted by different kinds of benzene derivatives. Acceptable correlations are obtained for the aquatic toxicity using quantum similarity derived descriptors, allowing a fairly confident classification of the studied compounds according to their toxicity level.
A flexible model for multivariate interval‐censored survival times with complex correlation structure
Authors: Falcaro Milena , Pickles Andrew 
Published: April 2006

AbstractWe focus on the analysis of multivariate survival times with highly structured interdependency and subject to interval censoring. Such data are common in developmental genetics and genetic epidemiology. We propose a flexible mixed probit model that deals naturally with complex but uninformative censoring. The recorded ages of onset are treated as possibly censored ordinal outcomes with the interval censoring mechanism seen as arising from a coarsened measurement of a continuous variable observed as falling between subject‐specific thresholds. This bypasses the requirement for the failure times to be observed as falling into non‐overlapping intervals. The assumption of a normal age‐of‐onset distribution of the standard probit model is relaxed by embedding within it a multivariate Box–Cox transformation whose parameters are jointly estimated with the other parameters of the model. Complex decompositions of the underlying multivariate normal covariance matrix of the transformed ages of onset become possible. The new methodology is here applied to a multivariate study of the ages of first use of tobacco and first consumption of alcohol without parental permission in twins. The proposed model allows estimation of the genetic and environmental effects that are shared by both of these risk behaviours as well as those that are specific. Copyright © 2006 John Wiley & Sons, Ltd.
A penalized likelihood approach to magnetic resonance image reconstruction
Authors: Bulaevskaya Vera L. , Oehlert Gary W. 
Published: April 2006

AbstractCurrently, images acquired via magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI) technology are reconstructed using the discrete inverse Fourier transform. While computationally convenient, this approach is not able to filter out noise. This is a serious limitation because the amount of noise in MRI and fMRI can be substantial. In this paper, we propose an alternative approach to reconstruction, based on penalized likelihood methodology. In particular, we focus on non‐linear shrinkage estimators and show that this approach achieves a great reduction in integrated mean squared error (IMSE) of the estimated image with respect to the currently used estimator. This approach is extremely fast and easy to implement computationally. In addition, it can be combined with various alternative approaches to MR image reconstruction and can be easily adapted to other, non‐MRI contexts, in which the observed data and the quantities of interest are related via a linear transform. Copyright © 2006 John Wiley & Sons, Ltd.
A method for therapeutic dose selection in a phase II clinical trial using contrast statistics
Authors: Wakana Akira , Yoshimura Isao , Hamada Chikuma 
Published: April 2006

AbstractThis paper proposes a statistical method for determining the therapeutic dose of a test drug in a confirmatory clinical trial based on a phase II clinical trial using 3 or 4 doses of the drug. This method assumes the primary variable has a normal distribution with a common variance, that a test‐drug effect is seen when the population means show a response pattern indicating a monotonic increase with dose, and that there is a prior distribution for the population means. Under the proposed method, multiple contrast statistics are determined, such as contrast statistics for linear increase and plateau, and a response pattern is selected based on the maximum contrast statistic. The posterior probability that the selected response pattern is the true one is evaluated, and if this exceeds the cut‐off value a therapeutic dose is selected based on the estimated response pattern. To select the appropriate cut‐off value, a simulation study was conducted using a loss function for which the loss due to overestimation is greater than the loss due to underestimation. It was found that, as a rule, the appropriate cut‐off value to reduce the expected loss for various response patterns is 0.75 for a 3‐group trial and 0.70 for a 4‐group trial. Using these cut‐off values, the proposed method was applied to a previous clinical trial of a leukotriene receptor antagonist in patients with bronchial asthma. The method enabled the selection of what are considered appropriate response patterns and a therapeutic dose. Thus, the proposed method appears reasonable. Copyright © 2006 John Wiley & Sons, Ltd.
A comparison of methods for the analysis of recurrent health outcome data with environmental covariates
Authors: Fung Karen Y. , Khan Shahedul , Krewski Daniel , Ramsay Tim 
Published: April 2006

AbstractRecurrent events such as repeated hospital admissions for the same health outcome occur frequently in environmental health studies. Dewanji and Moolgavkar proposed a flexible parametric model and a conditional likelihood analysis for recurrent events based on a Poisson process formulation. In this paper, we examine the statistical properties of the Dewanji–Moolgavkar (DM) estimator of the risk of an adverse health outcome associated with environmental exposures based on recurrent event data using computer simulation. We also compare the DM approach with both case–crossover analysis for multiple observations and time series analysis when there are no subject‐specific covariates. When using a correctly specified model, the DM method produced better estimates with respect to relative mean square error when each subject had constant or curved baseline intensity functions than it did when baseline intensities were increasing or decreasing in a linear fashion. For under‐specified models, the DM method outperformed case–crossover analysis for decreasing straight line intensity functions, was outperformed by case–crossover analysis for increasing straight line intensity functions, and was roughly equivalent to case–crossover analysis for constant and curved intensity functions. Case–crossover analysis produced superior risk estimates more frequently than the other two methods in the cases considered here, especially for linear representations of the baseline intensities. Copyright © 2006 John Wiley & Sons, Ltd.
Gaussianization‐based quasi‐imputation and expansion strategies for incomplete correlated binary responses
Authors: Demirtas Hakan , Hedeker Donald 
Published: April 2006

AbstractNew quasi‐imputation and expansion strategies for correlated binary responses are proposed by borrowing ideas from random number generation. The core idea is to convert correlated binary outcomes to multivariate normal outcomes in a sensible way so that re‐conversion to the binary scale, after performing multiple imputation, yields the original specified marginal expectations and correlations. This conversion process ensures that the correlations are transformed reasonably which in turn allows us to take advantage of well‐developed imputation techniques for Gaussian outcomes. We use the phrase ‘quasi’ because the original observations are not guaranteed to be preserved. We argue that if the inferential goals are well‐defined, it is not necessary to strictly adhere to the established definition of multiple imputation. Our expansion scheme employs a similar strategy where imputation is used as an intermediate step. It leads to proportionally inflated observed patterns, forcing the data set to a complete rectangular format. The plausibility of the proposed methodology is examined by applying it to a wide range of simulated data sets that reflect alternative assumptions on complete data populations and missing‐data mechanisms. We also present an application using a data set from obesity research. We conclude that the proposed method is a promising tool for handling incomplete longitudinal or clustered binary outcomes under ignorable non‐response mechanisms. Copyright © 2006 John Wiley & Sons, Ltd.
Supporting the analysis of clones in software systems
Authors: Kapser Cory J. , Godfrey Michael W. 
Published: April 2006

AbstractCode duplication is a well‐documented problem in industrial software systems. There has been considerable research into techniques for detecting duplication in software, and there are several effective tools to perform this task. However, there have been few detailed qualitative studies into how cloning actually manifests itself within software systems. This is primarily due to the large result sets that many clone‐detection tools return; these result sets are very difficult to manage without complementary tool support that can scale to the size of the problem, and this kind of support does not currently exist. In this paper we present an in‐depth case study of cloning in a large software system that is in wide use, the Apache Web server; we provide insights into cloning as it exists in this system, and we demonstrate techniques to manage and make effective use of the large result sets of clone‐detection tools. In our case study, we found several interesting types of cloning occurrences, such as ‘cloning hotspots’, where a single subsystem comprising only 17% of the system code contained 38.8% of the clones. We also found several examples of cloning behavior that were beneficial to the development of the system, in particular cloning as a way to add experimental functionality. Copyright © 2006 John Wiley & Sons, Ltd.
How do APIs evolve? A story of refactoring
Authors: Dig Danny , Johnson Ralph 
Published: April 2006

AbstractFrameworks and libraries change their APIs. Migrating an application to the new API is tedious and disrupts the development process. Although some tools and ideas have been proposed to solve the evolution of APIs, most updates are done manually. To better understand the requirements for migration tools, we studied the API changes of four frameworks and one library. We discovered that the changes that break existing applications are not random, but tend to fall into particular categories. Over 80% of these changes are refactorings. This suggests that refactoring‐based migration tools should be used to update applications. Copyright © 2006 John Wiley & Sons, Ltd.
Refactoring a legacy component for reuse in a software product line: a case study
Authors: Kolb Ronny , Muthig Dirk , Patzke Thomas , Yamauchi Kazuyuki 
Published: April 2006

AbstractProduct lines are a promising approach to improve conceptually the productivity of the software development process and thus to reduce both the cost and time of developing and maintaining increasingly complex systems. An important issue in the adoption of the product‐line approach is the migration of legacy software components, which have not been designed for reuse, systematically into reusable product‐line components. This article describes activities performed to improve systematically the design and implementation of an existing software component in order to reuse it in a software product line. The activities are embedded in the application of Fraunhofer PuLSE™‐DSSA—an approach for defining domain‐specific software architectures (DSSA) and product‐line architectures. The component under investigation is the so‐called Image Memory Handler (IMH), which is used in Ricoh's current products of office appliances such as copier machines, printers, and multi‐functional peripherals. It is responsible for controlling memory usage and compressing and decompressing image data. Improvement of both the component's design and implementation are based on a systematic analysis and focused on increasing maintainability and reusability and hence suitability for use in a product line. As a result of the analysis and refactoring activities, the documentation and implementation of the component has been considerably improved as shown by quantitative data collected at the end of the activities. Despite a number of changes to the code, the external behavior of the component has been preserved without significantly affecting the performance. Copyright © 2006 John Wiley & Sons, Ltd.
The first patient diagnosed with cytochrome c oxidase deficient Leigh syndrome: Progress report
Authors: Coenen M. J. H. , Smeitink J. A. M. , Farhoud M. H. , Nijtmans L. G. J. , Rodenburg R. , Janssen A. , van Kaauwen E. P. M. , Trijbels F. J. M. , van den Heuvel L. P. 
Published: April 2006

SummaryMutations in SURF1, an assembly gene for cytochrome c oxidase (COX), the fourth complex of the oxidative phosphorylation system, are most frequently encountered in patients with COX deficiency. We describe a patient with Leigh syndrome harbouring a mutation in SURF1 who was reported decades ago with a tissue‐specific cytochrome c oxidase deficiency.
Inefficient cleavage of palmitoyl‐protein thioesterase (PPT) substrates by aminothiols: Implications for treatment of infantile neuronal ceroid lipofuscinosis
Authors: Lu J.‐Y. , Hofmann S. L. 
Published: April 2006

SummaryInfantile neuronal ceroid lipofuscinosis (INCL, also known as infantile Batten disease) is a devastating neurodegenerative disorder caused by deficiency in the lysosomal enzyme palmitoyl‐protein thioesterase (PPT, or CLN1), which functions to remove long‐chain fatty acids from cysteine residues in proteins. A previous study suggested that the drug cysteamine, a simple aminothiol used in the treatment of cystinosis, may have utility in the treatment of INCL. In the current study, we compared the catalytic rate constants for the conversion of palmitoyl‐CoA (a PPT substrate) and cystine (which accumulates in cystinosis) by cysteamine. We found that while cysteamine can react with palmitoyl‐CoA, the rate constant is 103‐fold less than the reaction with cystine. Structure–activity studies suggested that it is the thiolate ion that is reactive in the cleavage reaction and that the amino group probably facilitates lysosomal entry. A modest effect of cysteamine (and two related aminothiols, WR 1065 and dimethylaminoethanethiol, DMAET) on PPT substrate accumulation in INCL lymphoblasts was observed. However, at optimum concentration a paradoxical increase in saposin immunoreactivity was seen, indicating possible lysosomal dysfunction. Improvements are needed in the design of small molecules for the treatment of INCL disease.
Dietary compliance in ornithine aminotransferase deficiency
Authors: Santos Lucia , Fiona White J. , Walter John H. 
Published: April 2006

SummaryOrnithine δ‐aminotransferase (OAT) deficiency (McKusick 258870) is associated with hyperornithinaemia, thought to be the cause of the progressive retinal degeneration that occurs in this disorder. For the large majority of cases unresponsive to the co‐factor pyridoxine, treatment is based on reducing ornithine plasma levels below 400 μ mol/L with an arginine‐restricted diet. This has been shown to slow the progression of retinal disease. (Santinelli et al 2004). In Table 1 we present our experience in the dietary management of 12 patients (7 female) from 8 families. Compliance was defined as good, intermediate or poor according to plasma ornithine levels. Only one patient could be categorized as a good complier, 5 were intermediate, and 6 were poor. The age at start of treatment was the most important factor as regards ability to comply with diet. Our study emphasizes the difficulty with dietary treatment and need for early diagnosis. For the older patients, alternative treatments such as the use of oral lysine to increase renal losses of ornithine need to be investigated further (Peltola et al 2000).
Cognitive reserve in neuropsychiatry
Authors: BARNETT J. H. , SALMOND C. H. , JONES P. B. , SAHAKIAN B. J. 
Published: April 2006

Background. The idea that superior cognitive function acts as a protective factor against dementia and the consequences of head injury is well established. Here we suggest the hypothesis that cognitive reserve is also important in neuropsychiatric disorders including schizophrenia, bipolar disorder and depression.Method. We review the history of passive and active models of reserve, and apply the concept to neuropsychiatric disorders. Schizophrenia is used as an exemplar because the effects of premorbid IQ and cognitive function in this disorder have been extensively studied.Results. Cognitive reserve may impact on neuropsychiatric disorders in three ways: by affecting the risk for developing the disorder, in the expression of symptoms within disorders, and in patients' functional outcome. Cognitive failure below a certain threshold may alone, or in combination with common psychiatric symptoms, produce neuropsychiatric syndromes.Conclusions. Consideration of cognitive reserve may considerably improve our understanding of individual differences in the causes and consequences of neuropsychiatric disorders. For these reasons, the concept of cognitive reserve should be incorporated in future studies of neuropsychiatric disorder. It may be possible to enhance cognitive reserve through pharmacological or non-pharmacological means, such as education, neurocognitive activation or other treatment programmes.
Transduction of biochemical signals across cell membranes
Authors: Hendrickson Wayne A. 
Published: April 2006

1. Introduction 3212. Tyrosine kinase receptors 3223. Histidine kinase sensors 3254. G-protein coupled receptors 3275. Principles 3286. Acknowledgments 3297. References 330Biological cells need to be responsive to various stimuli, primarily chemical ligands from their environments. Specific receptor molecules embedded in the plasma membrane detect the different biochemical signals that impact the cell, and these receptors are the conduits for transmission of this information to the cell interior for action. There are several classes of signal transduction receptors and many specific receptors within each of the major classes. This review emphasizes the structural biology of three major classes of transmembrane receptors – tyrosine kinase receptors, histidine kinase sensors, and G-protein coupled receptors. Biophysical principles that govern the processes of signal transduction across cell membranes are also discussed.
Addressing the challenges of cellular delivery and bioavailability of peptide nucleic acids (PNA)
Authors: Nielsen Peter E. 
Published: April 2006

1. Introduction 3452. Peptide nucleic acid (PNA) 3463. ‘Cell penetrating peptides’ (CPPs) 3464. Endosomal escape 3475. Cellular delivery of PNA 3476.In vivobioavailability of PNA 3497. References 350Recent results on the cellular delivery of antisense peptide nucleic acids (PNA) via peptide conjugation is briefly discussed, in particular in the context of endosomal entrapment and escape.
BBS: An Energy Efficient Localized Routing Scheme for Query Processing in Wireless Sensor Networks
Authors: Lian Jie , Naik Kshirasagar , Agnew Gordon B. , Chen Lei , Özsu M. Tamer 
Published: April 2006

A wireless sensor network (WSNET) can support various types of queries. The energy resource of sensors constrains the total number of query responses, called query capacity, received by the sink. There are four problems in the existing approaches for energy-efficient query processing in WSNETs: the fact that sensors near the sink drain their energy much faster than distant sensors has been overlooked, routing trees (RT) are rooted at the sink, and therefore, aggregative queries are less energy-efficient, data reception cost has been ignored, and flooding is used in query distribution or RT construction. In this paper, we propose a Broadcasting-Based query Scheme (BBS) to address the above problems. BBS reduces the energy depletion rate of sensors near the sink, builds different localized RTs for different query types, and eliminates the flooding cost of query distribution. Compared to the existing approaches, simulation studies show that BBS produces significant improvement in the query capacity for non-holistic queries (10%—100% capacity improvement) and holistic queries (up to an order of magnitude of capacity improvement).
MicroRouting: A Scalable and Robust Communication Paradigm for Sparse Ad Hoc Networks
Authors: Das Saumitra M. , Pucha Himabindu , Hu Y. Charlie 
Published: April 2006

Mobile ad hoc networks are self-organizing networks that provide rapid network connectivity in infrastructureless environments. Most routing protocols designed for MANETs assume connected networks. Such a restriction directly limits the application domains of MANETs. In this paper, we study the problem of providing time-critical data delivery in sparse ad hoc networks where network partition can last for a long period, without imposing any restrictions on the node mobility. Supporting real-time communication with unconstrained mobility is important to many mission-critical applications such as battlefields and search and rescue in large-scale disaster areas. In this paper, we propose microrouting networks consisting of tiny nodes similar to sensors but without transducers (called microrouters) as a substrate for time-critical data delivery in sparse MANETs. We describe the microrouting protocol for the resulting hybrid network which exploits the fact that microrouters are stationary, but are constrained by energy and memory. Key features of the microrouting protocol design include stateless architecture and localized route repair. We demonstrate the viability of the microrouting network architecture via detailed simulation evaluation. Our results show that microrouting networks running the microrouting protocol efficiently extend the connectivity of sparse MANETs and provide high packet delivery ratios.