bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Joined‐up Approach to User Participation in Public Services: Strengthening the “Participation Chain”
Authors: Simmons Richard , Birchall Johnston 
Published: May 2005

AbstractParticipation has emerged as a key theme for social policy and administration in the UK. Public service providers are often keen to consult users, and users themselves want to make their voices heard. Despite this, however, there is a perennial problem in getting people to participate, and participation is often better supported in principle than in practice. The motivations of key actors are crucial, but are often poorly understood. This article attempts to build a more detailed understanding of the motivations to participate of one key group: service users. Using Mutual Incentives Theory, it shows the extent to which users are motivated by individualistic or collectivistic concerns. These “demand side” factors are then combined with others on the “supply side” in a model we call the “participation chain”. This model provides a systematic framework for understanding what makes public service users participate, and seeks to demonstrate that, while the question of participation requires a combination of answers, it is a combination that can be predicted, planned for and acted upon.
The Clash of Voices: Community‐based Targeting of Safety‐net Interventions in Malawi
Authors: Chinsinga Blessings 
Published: May 2005

Abstract Using the principle of community targeting, the 2003 Winter Targeted Input Programme was designed to extend free inputs to about 400,000 households in rural Malawi on the basis of access to dambo, and poverty status. The tendency for most communities was, however, to modify the stipulated criteria on the basis of their perceptions and interpretations of need, entitlement and equity. Strikingly, even though the resulting criteria often reflected priorities conflicting with the officially prescribed guidelines, they were nevertheless not necessarily motivated by fraudulent intentions, though there were some isolated cases of ill‐intention. This article therefore advocates at least the incorporation of views from below in the design of interventions of this nature in order to ensure that they achieve the overall desired strategic impact.
Deviant Action and Self‐Narration: A Qualitative Survey through ATLAS.ti
Authors: PATRIZI PATRIZIA 
Published: May 2005

This paper has its roots in qualitative analysis of accounts produced by an Italian serial killer. Theoretical references are related to symbolic interactionism and its developments in the field of psychology and criminology. The whole contribution is aimed to twofold purposes: A) to provide a set of criteria specifically addressed to study deviant action as system of meanings into two related contexts: the single action itself and the whole life history. According this point, paper introduces the concept of “deviant career” and it explains its development and steps; it also provides some psychological social points of views and contributions that scientific works offers. B) to think about potentialities of accounting interviews as powerful tools in clinical practice and empirical research too.Specifically, we discuss narrative about behaviour and life story as a resource in order to take suggestions about meanings, goals and rules of action. It also suggests something about functions that crime discharges in the whole pathway of one's life. Juridical case analysis, run by means of the software ATLAS.ti, is aimed to demonstrate theoretical reasoning proposed.
c-Jun N-terminal kinase (JNK) is required for survival and proliferation of B-lymphoma cells
Authors: Gururajan Murali , Chui Roger , Karuppannan Anbu K. , Ke Jiyuan , Jennings C. Darrell , Bondada Subbarao 
Published: May 2005

AbstractSeveral primary murine and human B lymphomas and cell lines were found to constitutively express high levels of the activated form of c-jun N-terminal kinase (JNK), a member of the mitogen-activated protein (MAP) kinase family. Proliferation of murine B lymphomas CH31, CH12.Lx, BKS-2, and WEHI-231 and the human B lymphomas BJAB, RAMOS, RAJI, OCI-Ly7, and OCI-Ly10 was strongly inhibited by SP600125, an anthrapyrazolone inhibitor of JNK, in a dose-dependent manner. The lymphoma cells underwent apoptosis and arrested at the G2/M phase of cell cycle. Furthermore, JNK-specific small interfering RNA (siRNA) inhibited the growth of both murine and human B lymphomas. Thus in the B-lymphoma model, JNK appears to have a unique prosurvival role. Survival signals provided by CD40 and interleukin-10 (IL-10) together reversed the growth inhibition induced by the JNK inhibitor. c-Myc protein levels were reduced in the presence of both SP600125 and JNK-specific siRNA, and CD40 ligation restored c-Myc levels. Moreover, Bcl-xL rescued WEHI-231 cells from apoptosis induced by the JNK inhibitor. The JNK inhibitor also reduced levels of early growth response gene-1 (Egr-1) protein, and overexpressing Egr-1 partially rescued lymphoma cells from apoptosis. Thus, JNK may act via c-Myc and Egr-1, which were shown to be important for B-lymphoma survival and growth. (Blood. 2005;106:1382-1391)
Malaria-specific transgenic CD4+ T cells protect immunodeficient mice from lethal infection and demonstrate requirement for a protective threshold of antibody production for parasite clearance
Authors: Stephens Robin , Albano Frank R. , Quin Stuart , Pascal Benjamin J. , Harrison Vicky , Stockinger Brigitta , Kioussis Dimitris , Weltzien Hans-Ulrich , Langhorne Jean 
Published: May 2005

AbstractT cells are important in the immune response to malaria, both for their cytokines and their help for antibody production. To look at the relative importance of these roles, a T-cell receptor (TCR) transgenic mouse has been generated carrying a TCR specific for an epitope of the merozoite surface protein 1 (MSP-1) of the malaria parasite, Plasmodium chabaudi. In adoptive transfer experiments, malaria-specific CD4+ T cells expand and produce interferon γ (IFN-γ) early in infection, but the population contracts quickly despite prolonged persistence of the parasite. MSP-1-specific CD4+ cells can protect immunodeficient mice from lethal infection; however, the parasite is only completely cleared in the presence of B cells showing that T helper cells are critical. Levels of malaria-specific antibody and the speed of their production clearly correlate with the time of resolution of infection, indicating that a critical threshold of antibody production is required for parasite clearance. Furthermore, T cells specific for a shed portion of MSP-1 are able to provide help for antibody to the protective region, which remains bound to the infected erythrocyte, suggesting that MSP-1 has all of the components necessary for a good vaccine. (Blood. 2005;106:1676-1684)
Chimeric NK-receptor–bearing T cells mediate antitumor immunotherapy
Authors: Zhang Tong , Lemoi Bethany A. , Sentman Charles L. 
Published: May 2005

AbstractNKG2D is an activating cell-surface receptor expressed on natural killer (NK) cells and some T-cell subsets. Its ligands are primarily expressed on tumor cells. The aim of this study was to determine whether chimeric NK-receptor—bearing T cells would directly kill tumor cells and lead to induction of host immunity against tumors. Chimeric NK receptors were produced by linking NKG2D or DNAX activating protein of 10 kDa (Dap10) to the cytoplasmic portion of the CD3ζ chain. Our results showed that chimeric (ch) NKG2D-bearing T cells responded to NKG2D-ligand–bearing tumor cells (RMA/Rae-1β, EG7) but not to wild-type tumor cells (RMA). This response was dependent upon ligand expression on the target cells but not on expression of major histocompatibility complex (MHC) molecules, and the response could be blocked by anti-NKG2D antibodies. These T cells produced large amounts of T-helper 1 (Th1) cytokines and proinflammatory chemokines and killed ligand–expressing tumor cells. Adoptive transfer of chNKG2D-bearing T cells inhibited RMA/Rae-1β tumor growth in vivo. Moreover, mice that had remained tumor-free were resistant to subsequent challenge with the wild-type RMA tumor cells, suggesting the generation of immunity against other tumor antigens. Taken together, our findings indicate that modification of T cells with chimeric NKG2D receptors represents a promising approach for immunotherapy against cancer.
Overexpression of sphingosine kinase 1 is an oncogenic event in erythroleukemic progression
Authors: Le Scolan Erwan , Pchejetski Dimitri , Banno Yoshiko , Denis Nicole , Mayeux Patrick , Vainchenker William , Levade Thierry , Moreau-Gachelin Françoise 
Published: May 2005

Abstract
The erythroleukemia developed by spi-1/PU.1-transgenic mice is a model of multistage oncogenic process. Isolation of tumor cells representing discrete stages of leukemic progression enables the dissection of some of the critical events required for malignant transformation. To elucidate the molecular mechanisms of multistage leukemogenesis, we developed a microarray transcriptome analysis of nontumorigenic (HS1) and tumorigenic (HS2) proerythroblasts from spi-1-transgenic mice. The data show that transcriptional up-regulation of the sphingosine kinase gene (SPHK1) is a recurrent event associated with the tumorigenic phenotype of these transgenic proerythroblasts. SPHK1 is an enzyme of the metabolism of sphingolipids, which are essential in several biologic processes, including cell proliferation and apoptosis. HS1 erythroleukemic cells engineered to overexpress the SPHK1 protein exhibited growth proliferative advantage, increased clonogenicity, and resistance to apoptosis in reduced serum level by a mechanism involving activation of the extracellular signal-related kinases 1/2 (ERK1/2) and phosphatidylinositol 3-kinase (PI3K)/AKT pathways. In addition, SPHK1-overexpressing HS1 cells acquired tumorigenicity when engrafted in vivo. Finally, enforced expression of a dominant-negative mutant of SPHK1 in HS2 tumorigenic cells or treatment with a pharmacologic inhibitor reduced both cell growth and apoptosis resistance. Altogether, these data suggest that overexpression of the sphingosine kinase may represent an oncogenic event during the multistep progression of an erythroleukemia. (Blood. 2005;106:1808-1816)
Inhibition of APC anticoagulant activity on oxidized phospholipid by anti–β2-glycoprotein I monoclonal antibodies
Authors: Safa Omid , Esmon Charles T. , Esmon Naomi L. 
Published: May 2005

AbstractActivated protein C (APC) anticoagulant activity and the ability to be inhibited by auto-antibodies associated with thrombosis are strongly augmented by the presence of phosphatidylethanolamine (PE) and phospholipid oxidation. β2-glycoprotein I (β2-GPI) is a major antigen for antiphospholipid antibodies present in patients with the antiphospholipid syndrome. We therefore investigated whether anti–β2-GPI monoclonal antibodies (mAbs) could inhibit APC with similar membrane specificity. Five mouse mAbs that reacted with different epitopes on β2-GPI were examined. Each inhibited the PE-, phospholipid oxidation–dependent enhancement of APC anticoagulant activity and required antibody divalency. A chimeric APC that retains anticoagulant activity but is relatively unaffected by protein S, PE, or oxidation was not inhibited by the antibodies. In purified systems, anti–β2-GPI mAb inhibition of factor Va inactivation was greater in the presence of protein S and required β2-GPI. Surprisingly, although the mAbs did increase β2-GPI affinity for membranes, PE and oxidation had little influence on the affinity of the β2-GPI antibody complex for the membrane vesicles. We conclude that antibodies to β2-GPI inhibit APC function specifically and contribute to a hypercoaguable state by disrupting specific protein-protein interactions induced by oxidation of PE-containing membranes.
How do stem cells find their way home?
Authors: Lapidot Tsvee , Dar Ayelet , Kollet Orit 
Published: May 2005

AbstractMigration of hematopoietic stem cells through the blood, across the endothelial vasculature to different organs and to their bone marrow (BM) niches, requires active navigation, a process termed homing. Homing is a rapid process and is the first and essential step in clinical stem cell transplantation. Similarly, homing is required for seeding of the fetal BM by hematopoietic progenitors during development. Homing has physiological roles in adult BM homeostasis, which are amplified during stress-induced recruitment of leukocytes from the BM reservoir and during stem cell mobilization, as part of host defense and repair. Homing is thought to be a coordinated, multistep process, which involves signaling by stromal-derived factor 1 (SDF-1) and stem cell factor (SCF), activation of lymphocyte function–associated antigen 1 (LFA-1), very late antigen 4/5 (VLA-4/5) and CD44, cytoskeleton rearrangement, membrane type 1 (MT1)–matrix metalloproteinase (MMP) activation and secretion of MMP2/9. Rolling and firm adhesion of progenitors to endothelial cells in small marrow sinusoids under blood flow is followed by trans-endothelial migration across the physical endothelium/extracellular matrix (ECM) barrier. Stem cells finalize their homing uniquely, by selective access and anchorage to their specialized niches in the extravascular space of the endosteum region and in periarterial sites. This review is focused on mechanisms and key regulators of human stem cell homing to the BM in experimental animal models and clinical transplantation protocols.
Visualization methods for statistical analysis of microarray clusters
Authors: Hibbs Matthew A , Dirksen Nathaniel C , Li Kai , Troyanskaya Olga G 
Published: May 2005

Abstract
Background
The most common method of identifying groups of functionally related genes in microarray data is to apply a clustering algorithm. However, it is impossible to determine which clustering algorithm is most appropriate to apply, and it is difficult to verify the results of any algorithm due to the lack of a gold-standard. Appropriate data visualization tools can aid this analysis process, but existing visualization methods do not specifically address this issue.

Results
We present several visualization techniques that incorporate meaningful statistics that are noise-robust for the purpose of analyzing the results of clustering algorithms on microarray data. This includes a rank-based visualization method that is more robust to noise, a difference display method to aid assessments of cluster quality and detection of outliers, and a projection of high dimensional data into a three dimensional space in order to examine relationships between clusters. Our methods are interactive and are dynamically linked together for comprehensive analysis. Further, our approach applies to both protein and gene expression microarrays, and our architecture is scalable for use on both desktop/laptop screens and large-scale display devices. This methodology is implemented in GeneVAnD (Genomic Visual ANalysis of Datasets) and is available at http://function.princeton.edu/GeneVAnD.

Conclusion
Incorporating relevant statistical information into data visualizations is key for analysis of large biological datasets, particularly because of high levels of noise and the lack of a gold-standard for comparisons. We developed several new visualization techniques and demonstrated their effectiveness for evaluating cluster quality and relationships between clusters.
Predicting functional sites with an automated algorithm suitable for heterogeneous datasets
Authors: La David , Livesay Dennis R 
Published: May 2005

AbstractBackgroundIn a previous report (La et al.,Proteins, 2005), we have demonstrated that the identification of phylogenetic motifs, protein sequence fragments conserving the overall familial phylogeny, represent a promising approach for sequence/function annotation. Across a structurally and functionally heterogeneous dataset, phylogenetic motifs have been demonstrated to correspond to a wide variety of functional site archetypes, including those defined by surface loops, active site clefts, and less exposed regions. However, in our original demonstration of the technique, phylogenetic motif identification is dependent upon a manually determined similarity threshold, prohibiting large-scale application of the technique.ResultsIn this report, we present an algorithmic approach that determines thresholds without human subjectivity. The approach relies on significant raw data preprocessing to improve signal detection. Subsequently, Partition Around Medoids Clustering (PAMC) of the similarity scores assesses sequence fragments where functional annotation remains in question. The accuracy of the approach is confirmed through comparisons to our previous (manual) results and structural analyses. Triosephosphate isomerase and arginyl-tRNA synthetase are discussed as exemplar cases. A quantitative functional site prediction assessment algorithm indicates that the phylogenetic motif predictions, which require sequence information only, are nearly as good as those from evolutionary trace methods that do incorporate structure.ConclusionThe automated threshold detection algorithm has been incorporated into MINER, our web-based phylogenetic motif identification server. MINER is freely available on the web athttp://www.pmap.csupomona.edu/MINER/. Pre-calculated functional site predictions of the COG database and an implementation of the threshold detection algorithm, in the R statistical language, can also be accessed at the website.
Robust detection of periodic time series measured from biological systems
Authors: Ahdesmäki Miika , Lähdesmäki Harri , Pearson Ron , Huttunen Heikki , Yli-Harja Olli 
Published: May 2005

AbstractBackgroundPeriodic phenomena are widespread in biology. The problem of finding periodicity in biological time series can be viewed as a multiple hypothesis testing of the spectral content of a given time series. The exact noise characteristics are unknown in many bioinformatics applications. Furthermore, the observed time series can exhibit other non-idealities, such as outliers, short length and distortion from the original wave form. Hence, the computational methods should preferably be robust against such anomalies in the data.ResultsWe propose a general-purpose robust testing procedure for finding periodic sequences in multiple time series data. The proposed method is based on a robust spectral estimator which is incorporated into the hypothesis testing framework using a so-calledg-statistic together with correction for multiple testing. This results in a robust testing procedure which is insensitive to heavy contamination of outliers, missing-values, short time series, nonlinear distortions, and is completely insensitive to any monotone nonlinear distortions. The performance of the methods is evaluated by performing extensive simulations. In addition, we compare the proposed method with another recent statistical signal detection estimator that uses Fisher's test, based on the Gaussian noise assumption. The results demonstrate that the proposed robust method provides remarkably better robustness properties. Moreover, the performance of the proposed method is preferable also in the standard Gaussian case. We validate the performance of the proposed method on real data on which the method performs very favorably.ConclusionAs the time series measured from biological systems are usually short and prone to contain different kinds of non-idealities, we are very optimistic about the multitude of possible applications for our proposed robust statistical periodicity detection method.AvailabilityThe presented methods have been implemented in Matlab and in R. Codes are available on request. Supplementary material is available at:http://www.cs.tut.fi/sgn/csb/robustperiodic/.
Computing expectation values for RNA motifs using discrete convolutions
Authors: Lambert André , Legendre Matthieu , Fontaine Jean-Fred , Gautheret Daniel 
Published: May 2005

Abstract
Background
Computational biologists use Expectation values (E-values) to estimate the number of solutions that can be expected by chance during a database scan. Here we focus on computing Expectation values for RNA motifs defined by single-strand and helix lod-score profiles with variable helix spans. Such E-values cannot be computed assuming a normal score distribution and their estimation previously required lengthy simulations.

Results
We introduce discrete convolutions as an accurate and fast mean to estimate score distributions of lod-score profiles. This method provides excellent score estimations for all single-strand or helical elements tested and also applies to the combination of elements into larger, complex, motifs. Further, the estimated distributions remain accurate even when pseudocounts are introduced into the lod-score profiles. Estimated score distributions are then easily converted into E-values.

Conclusion
A good agreement was observed between computed E-values and simulations for a number of complete RNA motifs. This method is now implemented into the ERPIN software, but it can be applied as well to any search procedure based on ungapped profiles with statistically independent columns.
The integrins of the urochordate Ciona intestinalis provide novel insights into the molecular evolution of the vertebrate integrin family
Authors: Ewan Richard , Huxley-Jones Julie , Mould A Paul , Humphries Martin J , Robertson David L , Boot-Handford Raymond P 
Published: May 2005

Abstract

Background
Integrins are a functionally significant family of metazoan cell surface adhesion receptors. The receptors are dimers composed of an alpha and a beta chain. Vertebrate genomes encode an expanded set of integrin alpha and beta chains in comparison with protostomes such as drosophila or the nematode worm. The publication of the genome of a basal chordate, Ciona intestinalis, provides a unique opportunity to gain further insight into how and when the expanded integrin supergene family found in vertebrates evolved.

Results
The Ciona genome encodes eleven α and five β chain genes that are highly homologous to their vertebrate homologues. Eight of the α chains contain an A-domain that lacks the short alpha helical region present in the collagen-binding vertebrate alpha chains. Phylogenetic analyses indicate the eight A-domain containing α chains cluster to form an ascidian-specific clade that is related to but, distinct from, the vertebrate A-domain clade. Two Ciona α chains cluster in laminin-binding clade and the remaining chain clusters in the clade that binds the RGD tripeptide sequence. Of the five Ciona β chains, three form an ascidian-specific clade, one clusters in the vertebrate β1 clade and the remaining Ciona chain is the orthologue of the vertebrate β4 chain.

Conclusion
The Ciona repertoire of integrin genes provides new insight into the basic set of these receptors available at the beginning of vertebrate evolution. The ascidian and vertebrate α chain A-domain clades originated from a common precursor but radiated separately in each lineage. It would appear that the acquisition of collagen binding capabilities occurred in the chordate lineage after the divergence of ascidians.