bluuebunny/crossref_metadata_2025 huggingface dataset:
International Organizations and their Members
Authors: Blokker Niels
Published: November 2005

The law of international organizations is a field of study full of themes with variations. With respect to a number of key chapters in this field, such as the legal status of international organizations, their institutional structure, powers, decision-making and decisions, sanctions, fundamental principles exist or are being developed. These principles or themes have a large number of variations in the rules and practice of individual organizations. Like in music, the variations in themselves may be interesting as such, but they can only be fully appreciated by not losing sight of the theme. Like in music, the themes in themselves may be interesting as such, but they can only be fully appreciated by also listening carefully to the multicoloured variations. This contribution is devoted to a central theme of the law of international organizations: the relationship between an international organization and its members. Already in the early days of existence of international organizations, this topic has given rise to numerous questions. Many of these have now been answered, but sometimes resurface in contemporary variations. In addition there are new questions. It is useful to first explore briefly the meaning of the word "members". The English word "member" and the French "membre" are both derived from the Latin word "membrum", which means "part of the body". This meaning is important because it indicates clearly that members are part of a whole – a fact which takes us straight to one of the core questions addressed in this article. Members of an international organization are not just members, after all – like the members of a bridge club or a gardening club. In most cases, the members of international organizations are states. How then can members of an international organization be members of a whole when in most cases those members are sovereign states, even if the concept of sovereignty of states is no longer as absolute at it used to be? This is one of the major questions within the field of the law of international organizations. In order to examine this question, this contribution is divided into two parts. Section I will concentrate on the role of members vis-à-vis international organizations. In Section II the focus will shift to the whole of which the members are part; this Section will briefly look at some of the questions involved in giving a certain amount of autonomy to this whole.
Hencky Strain and Hencky Model: Extending History and Ongoing Tradition
Authors: Xiao H.
Published: November 2005

A finite strain measure and a Hookean type finite hyperelastic model based on it were introduced by H. Hencky (1928, 1929) about seventy‐five years ago. About tweenty‐five years later, an objective Eulerian equation of rate form was established by C. Truesdell (1952, 1955) for a rate type extension of Hooke’s law to finite deformations. Originating from these, a history is constantly extending and a tradition is continuing to develop in constitutive modeling of elastic and inelastic behaviour at finite deformations. In a short story consisting of five parts, we would like to relate selected episodes and events in some relevant aspects. Our main objective is to disclose unexpected, perhaps interesting, intrinsic relationships between these independent creations by two great masters and to expound how and why these relationships play essential roles in understanding and clarifying fundamental issues in Eulerian rate theories of finite elastoplasticity
Optimal Dynamic Topology Design of Continuum Structures with Random Parameters
Authors: Cui M T , Chen J J , Jiang P G
Published: November 2005

Considering the randomness of physical parameters of structural material, dynamic characteristic topology optimization mathematical model based on reliability of planar continuum structures is built in this paper. In which topology information variables of the structure are taken as design variables, minimizing the mean value of total structural weight as objective function and satisfying the reliability requirement of structural dynamic characteristic as constraints. In the process of optimization, the ESO method based on probability is adopted as solution strategy. At the same time, distribution function method is utilized to convert the reliability constraints into conventional constraints formally. A square thin plate with four sides fixed is used as an example to demonstrate the rationality and validity of the presented model.
A Partially Broken Piezoelectric Fiber in an Elastic Matrix
Authors: Wang B.L.
Published: November 2005

Piezoelectric ceramics are often combined with other materials to fabricate composites, which are used for constructions of intelligent systems. This paper is concerned with the fracture of a piezoelectric fiber embedded in an elastic matrix of finite radius. The fiber composite medium is subjected to the axially symmetric mechanical and electrical loads. Fourier and Hankel transforms are used to reduce the problem to the solution of a system of integral equations. Numerical solutions for the crack tip fields are obtained for various crack sizes and different piezoelectric fiber volume fractions. Both impermeable and permeable crack‐face electrical boundary conditions are considered. Applicability and effect of the crack‐face electrical boundary conditions are discussed.
Constitutive Equation of Concrete: Mesomechanical Isotropic Model
Authors: Kafka Vratislav , Vokoun David
Published: November 2005

The general concept of mesomechanical constitutive modeling developed by the first author is applied to the description of inelastic mechanical behavior of concrete under very complex loading in three orthogonal directions. Concrete is modeled as an isotropic heterogeneous medium consisting of elastic inclusions that are embedded in a plastically deforming and fracturing matrix. The fracturing process of the matrix results in cumulative damage, in changes of elastic moduli, and in volumetric expansion. It was the confrontation with the complex experimental data presented in this study that led us to a new version of the hypotheses on which our special model for concrete is based. Three kinds of deformation modes in different loading segments are differentiated: elastic‐plastic‐damaging deformation, elastic‐plastic deformation, and only elastic deformation. Criteria for distinguishing between these three kinds of deformation are newly formulated. The results of this isotropic mesoscale model are shown to agree reasonably well with the experimental data received for very complex loading paths.
A Unified Approach to Analytical and Numerical Modelling of Sintering
Authors: Pan Jingzhe , Ch’ng H.N.
Published: November 2005

This paper presents a unified framework to model the sintering process of fine powders. The framework is based on classical virtual power principle and its corresponding variational principle. Firstly, the classical models of solid state, viscous and liquid phase sintering are reproduced assuming single matter re‐distribution mechanism and using the virtual power principle as the starting point. Then we demonstrate how to obtain the governing equations for microstructural evolution using the variational principle. These provide a common thread through the existing sintering models. Finally a numerical solution scheme is briefly outlined for computer simulation of microstructural evolution using the variational principle as the starting point. The computer simulation can follow the entire sintering process from powder compact to fully dense solid and deal with fully couple multi‐physics processes involving all the possible underlying matter re‐distribution mechanisms. Several examples are provided to demonstrate the deep insights that can be gained into the sintering process by using the numerical tool.
Parallel Techniques for the Virtual Cell
Authors: Rajasekaran Sanguthevar , Ammar Reda A. , Cheriyan Betsy , Loew Leslie
Published: November 2005

The Virtual Cell is a simulation package created by the National Resource for Cell Analysis and Modeling (NRCAM). It enables users to model cell biological processes [1]. The core of the Virtual Cell is solving a system of PDEs. Sequential runs of the Virtual Cell can take large amounts of time and hence parallelization is needed. In this paper we present a parallel implementation of a model that is inspired by the one-dimensional version of the Virtual Cell. Our experimental results show that this parallelization is quite effective. In particular, the speedups we obtain are good implying that the parallel techniques employed could improve the performance of the Virtual Cell.
The Aggregate General Design Cycle as a Perspective on the Evolution of Computing Communities of Interest
Authors: Kuechler W. , Vaishnavi V. K. , Petter S.
Published: November 2005

The manner in which the research and development efforts of different groups, each focused on a different aspect of a single complex computing artifact (e.g., database), evolve and mutually support the development of the artifact as a whole has fascinated researchers, economists, and philosophers of science alike. In this paper we propose the Aggregate General Design Cycle (AGDC), an aggregated form of the General Design Cycle (GDC), as a predictive model of the evolution over time of a computing research community of interest. We begin by demonstrating that the GDC accurately depicts the progress of any individual research effort. We then propose that multiple research and development efforts on a theme, even when conducted by nominally distinct groups (i.e. computer science cf. information systems; academics cf. practitioners) are predicted by the AGDC. We provide support for the proposal through a longitudinal meta-bibliographic study of database research.
How Important are High-Level ab initio Treatments for the Interaction Dipole Moment and Polarizability of Hene?
Authors: Karamanis Panaghiotis , Maroulis George
Published: November 2005

We report calculations of the interaction dipole moment and polarizability for the HeNe heterodiatom. Our results are extracted from finite-field Møller-Plesset perturbation theory and coupled cluster calculations with a large, flexible Gaussian-type basis set. At post-Hartree-Fock level, the interaction dipole moment is method-sensitive for relatively short internuclear separations R/a0 while the interaction polarizability becomes rapidly method-insensitive for R/a0 > 2.5.
On Deploying Scientific Software within the Grid-TLSE Project
Authors: Caron Eddy , Desprez Frédéric , Daydé Michel , Hurault Aurélie , Pantel Marc
Published: November 2005

The main goal of the Grid-TLSE project is to design an expert site that provides an easy access to a number of sparse matrix solver packages allowing their comparative analysis on user-submitted problems, as well as on matrices from collections also available on the site. The site provide user assistance in choosing the right solver for its problems and appropriate values for the solver parameters. A computational Grid is used to deal with all the runs arising from user requests.

After an overview of the project, we discuss on some of the main difficulties we face in Grid- TLSE: considering the amount of softwares that will be available, facilitating to facilitate their deployment and their exploitation over a Grid is crucial. We make use of an abstract meta-data based description of solvers and have introduced the concept of scenario, i.e. a high-level user assistance description that provides ways of discovering automatically the most appropriate solvers based on their description. The scenarios are used for generating the dynamic workflows that will be executed over the Grid and take advantage of some of the features available in the DIET Grid middleware. We also report on the introduction of a semantic-based component model for efficient service trading.
FIT: A Fast Algorithm for Discovering Frequent Itemsets in Large Databases
Authors: Luo Jun , Rajasekaran Sanguthevar
Published: November 2005

Association rules mining is an important data mining problem that has been studied extensively. In this paper, a simple but Fast algorithm for Intersecting attributes lists using hash Tables (FIT) is presented. FIT is designed for efficiently computing all the frequent itemsets in large databases. It deploys an idea similar to Eclat but has a much better computational performance than Eclat due to two reasons: 1) FIT makes fewer total number of comparisons for each intersection operation between two attributes lists, and 2) FIT significantly reduces the total number of intersection operations. Our experimental results demonstrate that the performance of FIT is much better than that of Eclat and Apriori algorithms.
Iraq and the Limit of Freedom
Authors: Alkhafaji Abbass
Published: November 2005

This presentation highlights the changes that have taken place in Iraq in the past 2 years. Traditionally, Iraqi individuals have not judged people based on sectarian identity—Sunni and Shiite. Iraqis have lived side by side for years; they have respected each other and married each other without any complications in most cases. Indeed, many Iraqis come from mixed families or neighborhoods and enjoy the similarities and the differences such intermarriage brings. Since the global media and satellite news outlets have started to classify the Iraqis as Sunni, Shiite, and Kurd, the Arab media and news outlets, including this article, have adopted the same terminologies with serious reconsideration.
Blogs in Campaign Communication
Authors: Lawson-Borders Gracie , Kirk Rita
Published: November 2005

In Election 2004, campaign Weblogs—or blogs—became a standard feature of campaign Web sites. Monitoring the adaptation of emergent technological tools into political communication assists future generations of scholars to understand the genesis of communication applications and explore future uses. Blogs are online diaries where information is electronically posted, updated frequently, and presented in reverse chronological order. Three concourses of research provide insight into blogging as a political communication function: the investigation of the blog as a social diary, the analysis of blogs as organizing tools, and blogs viewed as a form of civic, participatory journalism. The authors do not claim that blogging had a significant impact on the 2004 election outcome. However, they do argue that its effective use has been demonstrated and emerging applications of the tool pave the way for future campaign communication, one the authors suggest will become a standard part of campaign communication.
Candidate Campaign E-Mail Messages in the Presidential Election 2004
Authors: Williams Andrew Paul , Trammell Kaye D.
Published: November 2005

Candidate e-mail messages play an increasing role in online, candidate-controlled media. E-mail messages allow candidates to directly contact voters, serving as political marketing tools. This study content analyzed the universe of campaign e-mail messages ( N = 78) from the Bush and Kerry campaigns during the general cycle of the 2004 presidential election. Results indicate that as key election events drew near, candidates increased the number of e-mail messages they sent. Direct address (using you) in the e-mail messages occurred at a statistically significant higher level than expected. Candidates used e-mail messages for promotion more often than opponent attacks. The study also investigated issue coverage, message strategy, and interactivity. The findings indicate that e-mail messages are potent instruments because they can be forwarded to myriad nonsubscribers. As such, candidate e-mail messages can be considered a form of viral marketing that offers a unique way to overcome the problem of selective exposure.
Lebanese Elections 2005 Version
Authors: Ajami Joseph
Published: November 2005

This analysis by an authority in Middle Eastern politics discusses the historic 2005 elections in Lebanon. Much attention has been devoted to Iraqi developments, but the election outcome in Lebanon may be a better indicator of the potential for democracy in the region. In reviewing what happened, the author assesses the impact of the assassination of former Prime Minister Rafic Hariri and the subsequent withdrawal of Syrian military forces from Lebanon. Although the author highlights the importance of major Christian political figures returning from exile and imprisonment, he warns that the future is still volatile.
An Intensive Supervision Program That Worked: Service Delivery, Professional Orientation, and Organizational Supportiveness
Authors: Paparozzi Mario A. , Gendreau Paul
Published: November 2005

This study examined the effect of treatment services, organizational supportiveness, and parole officer orientation on parolee recidivism. The sample consisted of 240 parolees enrolled in an intensive surveillance supervision program and 240 parolees undergoing traditional parole supervision. The participants were high-risk/high-need parolees. Three measures of parolee recidivism were used: (a) technical parole violation, (b) new conviction, and (c) revocation. These measures were examined by level of treatment services, organizational supportiveness, and the law enforcement/treatment orientation of intensive surveillance supervision program parole officers of which there were three classifications: (a) law enforcement, (b) balanced, and (c) social casework. The data support the view that intensive supervision programs that (a) provide more treatment to higher risk offenders, (b) employ parole officers with balanced law enforcement/social casework orientations, and (c) are implemented in supportive organizational environments may reduce recidivism from 10% to 30% depending on the comparisons being made.
Institutional Conditions and Prison Suicide: Conditional Effects of Deprivation and Overcrowding
Authors: Huey Meredith P. , Mcnulty Thomas L.
Published: November 2005

This article uses national data on prisons in the United States to examine the effects of deprivation, overcrowding, and their interaction on the likelihood of prison suicide. Our central argument is that overcrowding is a pivotal feature of prison environments that conditions the effects of deprivation. Findings provide substantial support for this hypothesis. For example, at low levels of overcrowding, minimum-security facilities evidence a lower probability of prison suicide, but at high levels, they are as likely to experience a suicide as their medium- and maximum-security counterparts. Theoretical and policy implications of the findings are discussed.!
The Antecedents and Consequences of Top Management Fraud
Authors: Zahra Shaker A. , Priem Richard L. , Rasheed Abdul A.
Published: November 2005

Fraud by top management is a topic that has stirred public interest, concern, and controversy. In this article, the authors analyze fraud by senior executives in terms of its nature, scope, antecedents, and consequences. They draw on the fields of psychology, sociology, economics, and criminology to identify societal-, industry, and firm-level antecedents of management fraud and the individual differences that enhance or neutralize the likelihood and degree of such fraud. The authors also review the consequences of management fraud on various stakeholder groups such as shareholders, debtholders, managers, local communities, and society.
Cross-Sector Partnerships to Address Social Issues: Challenges to Theory and Practice
Authors: Selsky John W. , Parker Barbara
Published: November 2005

Project-based cross-sector partnerships to address social issues (CSSPs) occur in four “arenas”: business-nonprofit, business-government, government-nonprofit, and trisector. Research on CSSPs is multidisciplinary, and different conceptual “platforms” are used: resource dependence, social issues, and societal sector platforms. This article consolidates recent literature on CSSPs to improve the potential for cross-disciplinary fertilization and especially to highlight developments in various disciplines for organizational researchers. A number of possible directions for future research on the theory, process, practice, method, and critique of CSSPs are highlighted. The societal sector platform is identified as a particularly promising framework for future research.
Diversified Business Groups and Corporate Refocusing in Emerging Economies
Authors: Hoskisson Robert E. , Johnson Richard A. , Tihanyi Laszlo , White Robert E.
Published: November 2005

As emerging economies have improved their economic institutions, the performance of many large business groups has been reduced because such groups acted as market-substitute mechanisms. Consequently, business groups have become increasingly involved in refocusing activities. The authors develop a framework in which such refocusing is explained as an attempt to balance overall transaction costs faced by groups with organization-specific costs in order to improve group performance. They examine external and internal factors that might lead to the initiation of refocusing and also explain why different ownership structures may affect the direction of that refocusing (e.g., related vs. unrelated diversification).
Status and Stratification Processes in Organizational Life
Authors: Ravlin Elizabeth C. , Thomas David C.
Published: November 2005

Although status and stratification processes have been studied extensively at the societal level in the sociology literature, they continue to be neglected in the study of management and organizational life. This review begins by questioning why this neglect has occurred. The authors then focus on the theoretical perspectives and empirical findings related to ascribed and achieved status, their interrelationships, how status hierarchies are established and maintained in organizational settings, and the role of culture in these processes. They conclude with an agenda for future research and implications for management practice.
Audio from orbit: The future of libraries for individuals who are blind or vision impaired
Authors: Steer Michael , Cheetham Leonie
Published: November 2005

Free library service is a component of the foundations of democracy, citizenship, economic and social development, scholarship and education, in progressive societies. The evolution of libraries for people who are blind or vision impaired is briefly discussed and an innovative project, a talking book and daily newspaper delivery system that transfers digital information to the user via satellite, is described.
Caught in the chasm: Literary representation and suicide among people with impaired vision
Authors: Bolt David
Published: November 2005

Both fictional and factual discourses have situated visual impairment in a causal relationship with suicide. The article compares samples of these discourses in order to suggest that the fiction may have some bearing on the facts. This alternative explanation becomes all the more thought-provoking when it is considered that not only visual impairment but visual restoration has been posited as a cause of suicide.
Perceptual perspective taking in children who are blind: The state of research and a single-case study
Authors: Brambring Michael
Published: November 2005

Perceptual perspective taking is regarded as a major milestone in sociocognitive development that sighted children have generally mastered by the age of 4-5 years. In children who are blind, however, most prior research reports a strong developmental delay of several years compared with sighted peers. After examining the current state of research, this article presents a single-case study of a congenitally blind 36-month-old girl. An analysis of her behavior in stills from a videotaped developmental testing sequence confirms that Level-1 perspective taking may be acquired at an earlier age than previous experimental research would suggest.
Do Business Improvement District Organizations Make a Difference?
Authors: Hoyt Lorlene M.
Published: November 2005

The business improvement district (BID) is an international, yet controversial, model for urban revitalization. This article contributes to the BID debate by identifying the theories that underpin the model, developing a conceptual framework that examines the linkages between crime theories and BID services, and—through the use of spatial and statistical methods of analysis—measuring the impact of BID organizations on criminal activity in and around commercial areas. Results show that lower property crime rates differentiate commercial areas with BID organizations from those without BIDs and that the lower rates are not matched by higher crime in surrounding blocks.
Urban poverty in Cape Town
Authors: de Swardt Cobus , Puoane Thandi , Chopra Mickey , du Toit Andries
Published: November 2005

This paper describes key findings of a household livelihood survey conducted in impoverished African settlements in Cape Town, one of Africa’s wealthiest cities. Poverty in these areas is strongly shaped by the history of the Eastern Cape’s adverse spatial incorporation into the South African economy. Migrants from the rural areas are highly dependent on and integrated into the increasingly monetized economy - but are simultaneously marginalized and adversely incorporated within it. Survey findings show the costs and implications of this failure of the formal economy to provide adequate livelihoods. While many eke out a living in a vital yet marginal informal economy, these strategies are thoroughly linked to and dependent on the income that can be secured through participation in the formal job market. Those who are unable to find a foothold in the urban economy are highly vulnerable and are at risk of being confined to long-term poverty traps.
The political and institutional blockages to good governance: the case of the Lyari expressway in Karachi
Authors: Hasan Arif
Published: November 2005

This paper describes the attempts by government agencies to build an expressway along the Lyari River in Karachi, and the struggles by the long-established communities, whose homes and livelihoods would be destroyed, for consultation and consideration of less damaging alternatives. Official proposals would destroy the livelihoods of 40,000 wage earners and the schools of 26,000 students, along with household and community investments worth some US$ 80 million. Government planners and politicians failed to follow official procedures to allow public discussions of the plans or to provide communities with details of how and when they might be affected. The paper also describes how political parties failed to respond to the concerns of the inhabitants who were their supporters, even as they recognized that these concerns were legitimate. With no consultative process that can resolve differences and make planning more pro-poor and pro-environment, powerful interests have been able to impose their decisions despite well-planned alternatives to official proposals, which are more effective, less costly and far less disruptive to Karachi’s economy. However, these alternatives are being discussed more widely, as community organizations formed by those affected by the plans work with local academics, researchers and NGOs - and as the middle class and the media begin to see the legitimacy of their concerns and the value of the alternatives they propose.
Sustaining Cuttack’s urban service improvements: exploring the levers
Authors: Pal Jitender
Published: November 2005

This paper explores concerns relating to the DFID-funded Cuttack Urban Services Improvement Project (CUSIP) in the state of Orissa, one of the most challenging areas of India with its constant exposure to floods, drought, famine and cyclones, and associated social, economic and political complexities. It describes the achievements of the project, both in terms of infrastructure “hardware” and social “software” benefits, which are equally part of the “new infrastructure agenda”. It also points to reasons for the failure to achieve all of the original project targets in terms of coverage, upgrading provision of basic services, and linking them to citywide networks. It raises, in particular, post-project sustainability issues relating to the management of the increased infrastructure asset base that resulted from the project. Recommendations for action at both the municipal and community levels are presented, for immediate management of post-project issues involving institution building, and retaining and revitalizing the existing institutions.
Sequential analysis of surfactant, lung function and inflammation in cystic fibrosis patients
Authors: Griese Matthias , Essl Robert , Schmidt Reinhold , Ballmann Manfred , Paul Karl , Rietschel Ernst , Ratjen Felix ,   the Beat Study Group
Published: November 2005

Background

In a cross-sectional analysis of cystic fibrosis (CF) patients with mild lung disease, reduced surfactant activity was correlated to increased neutrophilic airway inflammation, but not to lung function. So far, longitudinal measurements of surfactant function in CF patients are lacking and it remains unclear how these alterations relate to the progression of airway inflammation as well as decline in pulmonary function over time.

Methods

As part of the BEAT trial, a longitudinal study to assess the course of airway inflammation in CF, we studied lung function, surfactant function and endobronchial inflammation using bronchoalveolar lavage fluid from 20 CF patients with normal pulmonary function (median FEV194% of predicted) at three times over a three year period.

Results

There was a progressive loss of surfactant function, assessed as minimal surface tension. The decline in surfactant function was negatively correlated to an increase in neutrophilic inflammation and a decrease in lung function, assessed by FEV1, MEF75/25%VC, and MEF25%VC. The concentrations of the surfactant specific proteins A, C and D did not change, whereas SP-B increased during this time period.

Conclusion

Our findings suggest a link between loss of surfactant function driven by progressive airway inflammation and loss of small airway function in CF patients with limited lung disease.
Identification of clustered microRNAs using an ab initio prediction method
Authors: Sewer Alain , Paul Nicodème , Landgraf Pablo , Aravin Alexei , Pfeffer Sébastien , Brownstein Michael J , Tuschl Thomas , van Nimwegen Erik , Zavolan Mihaela
Published: November 2005

Background

MicroRNAs (miRNAs) are endogenous 21 to 23-nucleotide RNA molecules that regulate protein-coding gene expression in plants and animals via the RNA interference pathway. Hundreds of them have been identified in the last five years and very recent works indicate that their total number is still larger. Therefore miRNAs gene discovery remains an important aspect of understanding this new and still widely unknown regulation mechanism. Bioinformatics approaches have proved to be very useful toward this goal by guiding the experimental investigations.

Results

In this work we describe our computational method for miRNA prediction and the results of its application to the discovery of novel mammalian miRNAs. We focus on genomic regions around already known miRNAs, in order to exploit the property that miRNAs are occasionally found in clusters. Starting with the known human, mouse and rat miRNAs we analyze 20 kb of flanking genomic regions for the presence of putative precursor miRNAs (pre-miRNAs). Each genome is analyzed separately, allowing us to study the species-specific identity and genome organization of miRNA loci. We only use cross-species comparisons to make conservative estimates of the number of novel miRNAs. Our ab initio method predicts between fifty and hundred novel pre-miRNAs for each of the considered species. Around 30% of these already have experimental support in a large set of cloned mammalian small RNAs. The validation rate among predicted cases that are conserved in at least one other species is higher, about 60%, and many of them have not been detected by prediction methods that used cross-species comparisons. A large fraction of the experimentally confirmed predictions correspond to an imprinted locus residing on chromosome 14 in human, 12 in mouse and 6 in rat. Our computational tool can be accessed on the world-wide-web.

Conclusion

Our results show that the assumption that many miRNAs occur in clusters is fruitful for the discovery of novel miRNAs. Additionally we show that although the overall miRNA content in the observed clusters is very similar across the three considered species, the internal organization of the clusters changes in evolution.
A rigorous method for multigenic families' functional annotation: the peptidyl arginine deiminase (PADs) proteins family example
Authors: Balandraud N , Gouret P , Danchin EGJ , Blanc M , Zinn D , Roudier J , Pontarotti P
Published: November 2005

Background

large scale and reliable proteins' functional annotation is a major challenge in modern biology. Phylogenetic analyses have been shown to be important for such tasks. However, up to now, phylogenetic annotation did not take into account expression data (i.e. ESTs, Microarrays, SAGE, ...). Therefore, integrating such data, like ESTs in phylogenetic annotation could be a major advance in post genomic analyses. We developed an approach enabling the combination of expression data and phylogenetic analysis. To illustrate our method, we used an example protein family, the peptidyl arginine deiminases (PADs), probably implied in Rheumatoid Arthritis.

Results

the analysis was performed as follows: we built a phylogeny of PAD proteins from the NCBI's NR protein database. We completed the phylogenetic reconstruction of PADs using an enlarged sequence database containing translations of ESTs contigs. We then extracted all corresponding expression data contained in EST database This analysis allowed us 1/ To extend the spectrum of homologs-containing species and to improve the reconstruction of genes' evolutionary history. 2/ To deduce an accurate gene expression pattern for each member of this protein family. 3/ To show a correlation between paralogous sequences' evolution rate and pattern of tissular expression.

Conclusion

coupling phylogenetic reconstruction and expression data is a promising way of analysis that could be applied to all multigenic families to investigate the relationship between molecular and transcriptional evolution and to improve functional annotation.
A non-parametric framework for estimating threshold limit values
Authors: Salanti Georgia , Ulm Kurt
Published: November 2005

Background

To estimate a threshold limit value for a compound known to have harmful health effects, an 'elbow' threshold model is usually applied. We are interested on non-parametric flexible alternatives.

Methods

We describe how a step function model fitted by isotonic regression can be used to estimate threshold limit values. This method returns a set of candidate locations, and we discuss two algorithms to select the threshold among them: the reduced isotonic regression and an algorithm considering the closed family of hypotheses. We assess the performance of these two alternative approaches under different scenarios in a simulation study. We illustrate the framework by analysing the data from a study conducted by the German Research Foundation aiming to set a threshold limit value in the exposure to total dust at workplace, as a causal agent for developing chronic bronchitis.

Results

In the paper we demonstrate the use and the properties of the proposed methodology along with the results from an application. The method appears to detect the threshold with satisfactory success. However, its performance can be compromised by the low power to reject the constant risk assumption when the true dose-response relationship is weak.

Conclusion

The estimation of thresholds based on isotonic framework is conceptually simple and sufficiently powerful. Given that in threshold value estimation context there is not a gold standard method, the proposed model provides a useful non-parametric alternative to the standard approaches and can corroborate or challenge their findings.
Hypothyroidism attenuates protein tyrosine nitration, oxidative stress and renal damage induced by ischemia and reperfusion: effect unrelated to antioxidant enzymes activities
Authors: Tenorio-Velázquez Verónica M , Barrera Diana , Franco Martha , Tapia Edilia , Hernández-Pando Rogelio , Medina-Campos Omar Noel , Pedraza-Chaverri José
Published: November 2005

Background

It has been established that hypothyroidism protects rats against renal ischemia and reperfusion (IR) oxidative damage. However, it is not clear if hypothyroidism is able to prevent protein tyrosine nitration, an index of nitrosative stress, induced by IR or if antioxidant enzymes have involved in this protective effect. In this work it was explored if hypothyroidism is able to prevent the increase in nitrosative and oxidative stress induced by IR. In addition the activity of the antioxidant enzymes catalase, glutathione peroxidase, and superoxide dismutase was studied. Control and thyroidectomized (HTX) rats were studied 24 h of reperfusion after 60 min ischemia.

Methods

Male Wistar rats weighing 380 ± 22 g were subjected to surgical thyroidectomy. Rats were studied 15 days after surgery. Euthyroid sham-operated rats were used as controls (CT). Both groups of rats underwent a right kidney nephrectomy and suffered a 60 min left renal ischemia with 24 h of reperfusion. Rats were divided in four groups: CT, HTX, IR and HTX+IR. Rats were sacrificed and samples of plasma and kidney were obtained. Blood urea nitrogen (BUN) and creatinine were measured in blood plasma. Kidney damage was evaluated by histological analysis. Oxidative stress was measured by immunohistochemical localization of protein carbonyls and 4-hydroxy-2-nonenal modified proteins. The protein carbonyl content was measured using antibodies against dinitrophenol (DNP)-modified proteins. Nitrosative stress was measured by immunohistochemical analysis of 3-nitrotyrosine modified proteins. The activity of the antioxidant enzymes catalase, glutathione peroxidase, and superoxide dismutase was measured by spectrophotometric methods. Multiple comparisons were performed with ANOVA followed by Bonferroni t test.

Results

The histological damage and the rise in plasma creatinine and BUN induced by IR were significantly lower in HTX+IR group. The increase in protein carbonyls and in 3-nitrotyrosine and 4-hydroxy-2-nonenal modified proteins was prevented in HTX+IR group. IR-induced decrease in renal antioxidant enzymes was essentially not prevented by HTX in HTX+IR group.

Conclusion

Hypothyroidism was able to prevent not only oxidative but also nitrosative stress induced by IR. In addition, the antioxidant enzymes catalase, glutathione peroxidase, and superoxide dismutase seem not to play a protective role in this experimental model.
TOIB Study. Are topical or oral ibuprofen equally effective for the treatment of chronic knee pain presenting in primary care: a randomised controlled trial with patient preference study. [ISRCTN79353052]
Authors: Cross Pamela L , Ashby Deborah , Harding Geoff , Hennessy Enid M , Letley Louise , Parsons Suzanne , Spencer Anne E , Underwood Martin ,   the TOIB Study Team
Published: November 2005

Background

Many older people have chronic knee pain. Both topical and oral non- steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat this. Oral NSAIDS are effective, at least in the short term, but can have severe adverse effects. Topical NSAIDs also appear to be effective, at least in the short term. One might expect topical NSAIDs both to be less effective and to have fewer adverse effects than oral NSAIDs. If topical NSAIDs have fewer adverse effects this may outweigh both the reduction in effectiveness and the higher cost of topical compared to oral treatment. Patient preferences may influence the comparative effectiveness of drugs delivered via different routes.

Methods

TOIB is a randomised trial comparing topical and oral ibuprofen, with a parallel patient preference study. We are recruiting people aged 50 or over with chronic knee pain, from 27 MRC General Practice Research Framework practices across the UK. We are seeking to recruit 283 participants to the RCT and 379 to the PPS. Participants will be followed up for up to two years (with the majority reaching one year). Outcomes will be assessed by postal questionnaire, nurse examination, laboratory tests and medical record searches at one and two years or the end of the study.

Discussion

This study will provide new evidence on the overall costs and benefits of treating chronic knee pain with either oral or topical ibuprofen. The use of a patient preference design is unusual, but will allow us to explore how preference influences response to a medication. In addition, it will provide more information on adverse events. This study will provide evidence to inform primary care practitioners, and possibly influence practice.
Mapping and characterization of the amplicon near APOA2 in 1q23 in human sarcomas by FISH and array CGH
Authors: Kresse Stine H , Berner Jeanne-Marie , Meza-Zepeda Leonardo A , Gregory Simon G , Kuo Wen-Lin , Gray Joe W , Forus Anne , Myklebost Ola
Published: November 2005

Background

Amplification of the q21-q23 region on chromosome 1 is frequently found in sarcomas and a variety of other solid tumours. Previous analyses of sarcomas have indicated the presence of at least two separate amplicons within this region, one located in 1q21 and one located near the apolipoprotein A-II (APOA2) gene in 1q23. In this study we have mapped and characterized the amplicon in 1q23 in more detail.

Results

We have used fluorescence in situ hybridisation (FISH) and microarray-based comparative genomic hybridisation (array CGH) to map and define the borders of the amplicon in 10 sarcomas. A subregion of approximately 800 kb was identified as the core of the amplicon. The amplification patterns of nine possible candidate target genes located to this subregion were determined by Southern blot analysis. The genes activating transcription factor 6 (ATF6) and dual specificity phosphatase 12 (DUSP12) showed the highest level of amplification, and they were also shown to be over-expressed by quantitative real-time reverse transcription PCR (RT-PCR). In general, the level of expression reflected the level of amplification in the different tumours. DUSP12 was expressed significantly higher than ATF6 in a subset of the tumours. In addition, two genes known to be transcriptionally activated by ATF6, glucose-regulated protein 78 kDa and -94 kDa (GRP78 and GRP94), were shown to be over-expressed in the tumours that showed over-expression of ATF6.

Conclusion

ATF6 and DUSP12 seem to be the most likely candidate target genes for the 1q23 amplification in sarcomas. Both genes have possible roles in promoting cell growth, which makes them interesting candidate targets.
The pp24 phosphoprotein of Mason-Pfizer monkey virus contributes to viral genome packaging
Authors: Bohl Christopher R , Brown Shanna M , Weldon Robert A
Published: November 2005

Background

The Gag protein of Mason-Pfizer monkey virus, a betaretrovirus, contains a phosphoprotein that is cleaved into the Np24 protein and the phosphoprotein pp16/18 during virus maturation. Previous studies by Yasuda and Hunter (J. Virology. 1998. 72:4095–4103) have demonstrated that pp16/18 contains a viral late domain required for budding and that the Np24 protein plays a role during the virus life cycle since deletion of this N-terminal domain blocked virus replication. The function of the Np24 domain, however, is not known.

Results

Here we identify a region of basic residues (KKPKR) within the Np24 domain that is highly conserved among the phosphoproteins of various betaretroviruses. We show that this KKPKR motif is required for virus replication yet dispensable for procapsid assembly, membrane targeting, budding and release, particle maturation, or viral glycoprotein packaging. Additional experiments indicated that deletion of this motif reduced viral RNA packaging 6–8 fold and affected the transient association of Gag with nuclear pores.

Conclusion

These results demonstrate that the Np24 domain plays an important role in RNA packaging and is in agreement with evidence that suggests that correct intracellular targeting of Gag to the nuclear compartment is an fundamental step in the retroviral life cycle.
Is albumin administration in the acutely ill associated with increased mortality? Results of the SOAP study
Authors: Vincent Jean-Louis , Sakr Yasser , Reinhart Konrad , Sprung Charles L , Gerlach Herwig , Ranieri V Marco ,   the 'Sepsis Occurrence in Acutely Ill Patients' investigators
Published: November 2005

Introduction

Albumin administration in the critically ill has been the subject of some controversy. We investigated the use of albumin solutions in European intensive care units (ICUs) and its relationship to outcome.

Methods

In a cohort, multicenter, observational study, all patients admitted to one of the participating ICUs between 1 May and 15 May 2002 were followed up until death, hospital discharge, or for 60 days. Patients were classified according to whether or not they received albumin at any time during their ICU stay.

Results

Of 3,147 admitted patients, 354 (11.2%) received albumin and 2,793 (88.8%) did not. Patients who received albumin were more likely to have cancer or liver cirrhosis, to be surgical admissions, and to have sepsis. They had a longer length of ICU stay and a higher mortality rate, but were also more severely ill, as manifested by higher simplified acute physiology score (SAPS) II and sequential organ failure assessment (SOFA) scores than the other patients. A Cox proportional hazard model indicated that albumin administration was significantly associated with decreased 30-day survival. Moreover, in 339 pairs matched according to a propensity score, ICU and hospital mortality rates were higher in the patients who had received albumin than in those who had not (34.8 versus 20.9% and 41.3 versus 27.7%, respectively, both p < 0.001).

Conclusion

Albumin administration was associated with decreased survival in this population of acutely ill patients. Further prospective randomized controlled trials are needed to examine the effects of albumin administration in sub-groups of acutely ill patients.
Nutmeg intoxication in Texas, 1998–2004
Authors: Forrester Mathias B.
Published: November 2005

Nutmeg is a spice that contains volatile oils comprised of alkyl benzene derivatives (myristicin, elemicin, safrole, etc.), terpenes and myristic acid. Nutmeg has a long history of abuse. This study describes the nutmeg ingestion calls received by Texas poison centers from 1998 to 2004. There were 17 calls involving nutmeg ingestion, of which 64.7% involved intentional abuse. When abuse and non-abuse ingestions were compared, abuse ingestions were more likely to involve males (100 versus 66.7%) and adolescents (55.6 versus 16.7%). The majority of both abuse and non-abuse calls were managed outside of health care facilities (54.5 and 66.7%, respectively). None of the ingestions resulted in more than moderate clinical effects or death.