bluuebunny/crossref_metadata_2025_split huggingface dataset:
Civic and social integration
Authors: Nash Mary , Wong John , Trlin Andrew 
Published: June 2006

English New Zealand research into social work experience with immigrants, refugees and asylum seekers supports international claims that a new field of practice is emerging. Migration across frontiers for social, political and economic reasons brings local social workers into contact with clients from all over the world as they struggle to settle into their new communities. Social workers in this field need to be skilled in work at all levels, micro, meso and macro. French Les recherches conduites en Nouvelle Zélande portant sur les expériences de travail social auprès des immigrants, des réfugiés et des demandeurs d'asile supportent les affirmations internationales à savoir qu'un nouveau champ de pratique est en émergence. Les migrations par-delà les frontières nationales pour des raisons sociales, politiques et économiques entraînent des contacts entre des travailleurs sociaux locaux et des clients en provenance du monde entier lorsque ceux-ci tentent de s'établir dans leurs nouvelles communautés. Les travailleurs sociaux dans ce champ de pratique doivent Átre outillés pour travailler à tous les niveaux car les cas qu'ils auront à traiter impliquent du travail à niveaux micro, méso et macro. Spanish La investigación en Nueva Zelanda sobre la experiencia del trabajo social con inmigrantes, refugiados y solicitantes de asilo apoya la creencia internacional que éste es un nuevo campo de práctica. Los movimientos migratorios por razones sociales, políticas, y económicas ponen a los trabajadores sociales locales en contacto con clientes provenientes de todo el mundo mientras éstos luchan por asentarse en sus nuevas comunidades. Los trabajadores sociales en este campo necesitan destrezas en todos los niveles, puesto que los casos frecuentemente necesitarán intervenciones en niveles micro, meso y macro.
The impact of a social work study abroad program in Australia on multicultural learning
Authors: Fairchild Sherry R. , Pillai Vijayan K. , Noble Carolyn 
Published: June 2006

English Internationalizing the US social work curriculum with programs of study abroad is an effective method to develop students’ awareness of the importance of global interdependence and increase multicultural knowledge. Results from the Multicultural Awareness/Knowledge/Skill Survey and pre-post focus groups indicate the merits of a US-Australian social work program of study abroad for master’s-level social work students. French Internationaliser le curriculum américain en travail social par le biais de programmes d'études à l'étranger est un moyen efficace pour prendre conscience de l'importance de l'interdépendance globale et pour hausser nos connaissances multiculturelles. Les résultats du sondage sur les degrés de conscience, de connaissances et d'habiletés multiculturelles ainsi que les résultats des entrevues en 'focus groups' pré et post expérience, révèlent les mérites d'un programme d'étude de maítrise à l'étranger en travail social dans un échange entre les Ütats-Unis et l'Australie. Spanish Una manera eficaz de desarrollar el sentido de interdependencia global y aumentar el conocimiento de asuntos multiculturales es a través de planes de estudio que incorporen temas internacionales y con programas en países fuera del propio. Los resultados de la encuesta Conciencia Multicultural/Conocimiento/Destrezas, y los grupos de pre y post focus señalan los méritos que tienen en este sentido los programas internacionales de master's de trabajo social entre EE.UU. y Australia.
Initiation of plasminogen activation on the surface of monocytes expressing the type II transmembrane serine protease matriptase
Authors: Kilpatrick Lynette M. , Harris Roger L. , Owen Kate A. , Bass Rosemary , Ghorayeb Christine , Bar-Or Amit , Ellis Vincent 
Published: June 2006

AbstractuPA (urokinase-type plasminogen activator) activates plasminogen with high efficiency when bound to its cellular receptor uPAR, but only after a prolonged lag phase during which generated plasmin activates pro-uPA. How the activity of this proteolytic system might be rapidly initiated is unknown. We have now found that 2 monocytic cell lines display distinct patterns of plasminogen activation. U937 cells, but not THP-1 cells, displayed the expected lag phase, suggesting a constitutive initiation mechanism on the latter. This was shown to be due to the plasmin-independent activation of uPAR-bound pro-uPA by a cell surface-associated protease and to correlate with the expression of matriptase, a type II transmembrane serine protease that was highly expressed in THP-1 cells but undetectable in U937 cells. Kinetic analysis demonstrated that matriptase is a relatively poor activator of pro-uPA in solution, approximately 100-fold less efficient than plasmin (kcat/Km 1.16 × 105 M-1s-1 cf 1.21 × 107 M-1s-1). However, down-regulation of matriptase expression in THP-1 cells by siRNA reduced the activation of cell-associated pro-uPA and the subsequent rapid initiation of plasminogen activation by 76% to 93%. Matriptase was also found to be expressed by peripheral blood monocytes and may therefore be a specific mechanism for the rapid initiation and regulation of plasminogen activation by these cells.
Gene expression of tumor angiogenesis dissected: specific targeting of colon cancer angiogenic vasculature
Authors: van Beijnum Judy R. , Dings Ruud P. , van der Linden Edith , Zwaans Bernadette M. M. , Ramaekers Frans C. S. , Mayo Kevin H. , Griffioen Arjan W. 
Published: June 2006

AbstractCrucial to designing angiostatic and vascular targeting agents is the identification of target molecules. Because angiogenesis is not limited to pathologic conditions, careful evaluation of putative therapeutic targets is warranted to prevent adverse effects associated with impaired physiologic angiogenesis. To identify tumor-specific angiogenesis markers, we compared transcriptional profiles of angiogenic endothelial cells isolated from malignant and nonmalignant tissues with those of resting endothelial cells. We identified 17 genes that showed specific overexpression in tumor endothelium but not in angiogenic endothelium of normal tissues, creating a therapeutic window for tumor vasculature-specific targeting. Antibody targeting of 4 cell-surface–expressed or secreted products (vimentin, CD59, HMGB1, IGFBP7) inhibited angiogenesis in vitro and in vivo. Finally, targeting endothelial vimentin in a mouse tumor model significantly inhibited tumor growth and reduced microvessel density. Our results demonstrate the usefulness of the identification and subsequent targeting of specific tumor endothelial markers for anticancer therapy.
Dangerous small B-cell clones
Authors: Merlini Giampaolo , Stone Marvin J. 
Published: June 2006

AbstractThe detection of a monoclonal immunoglobulin in serum or urine usually raises concerns about the size of the underlying B-cell-derived clone and possible systemic effects caused by its expansion. However, a small clone can synthesize a very toxic protein, producing devastating systemic damage and protean clinical presentations. The resulting “monoclonal component-related diseases,” although difficult to diagnose, may be progressive and even fatal. The monoclonal protein can aggregate and deposit systemically as occurs in light-chain amyloidosis, monoclonal immunoglobulin deposition disease, crystal-storing histiocytosis, and monoclonal cryoglobulinemia. Alternatively, some monoclonal proteins possess antibody activity toward autogenous antigens and cause chronic cold agglutinin disease, mixed cryoglobulinemia, and peripheral neuropathies. Other humoral mediators may contribute to neuropathy in variant disorders such as the POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome. The clone synthesizing the noxious monoclonal proteins is often small, and sensitive techniques may be required to detect these immunoglobulins. A delay in diagnosis can allow irreversible organ damage and dramatically shorten survival. Prompt recognition of suggestive signs and symptoms should trigger a thorough diagnostic approach to reach the correct diagnosis quickly, because this is the key to effective therapy. Although the treatment of these conditions is not optimal, significant advances have been made, improving the duration and quality of life.
Granzyme B, a novel mediator of allergic inflammation: its induction and release in blood basophils and human asthma
Authors: Tschopp Cornelia M. , Spiegl Nicole , Didichenko Svetlana , Lutmann Werner , Julius Peter , Virchow J. Christian , Hack C. Erik , Dahinden Clemens A. 
Published: June 2006

AbstractHistamine, leukotriene C4, IL-4, and IL-13 are major mediators of allergy and asthma. They are all formed by basophils and are released in particularly large quantities after stimulation with IL-3. Here we show that supernatants of activated mast cells or IL-3 qualitatively change the makeup of granules of human basophils by inducing de novo synthesis of granzyme B (GzmB), without induction of other granule proteins expressed by cytotoxic lymphocytes (granzyme A, perforin). This bioactivity of IL-3 is not shared by other cytokines known to regulate the function of basophils or lymphocytes. The IL-3 effect is restricted to basophil granulocytes as no constitutive or inducible expression of GzmB is detected in eosinophils or neutrophils. GzmB is induced within 6 to 24 hours, sorted into the granule compartment, and released by exocytosis upon IgE-dependent and -independent activation. In vitro, there is a close parallelism between GzmB, IL-13, and leukotriene C4 production. In vivo, granzyme B, but not the lymphoid granule marker granzyme A, is released 18 hours after allergen challenge of asthmatic patients in strong correlation with interleukin-13. Our study demonstrates an unexpected plasticity of the granule composition of mature basophils and suggests a role of granzyme B as a novel mediator of allergic diseases.
Impaired dendritic-cell function in ectodermal dysplasia with immune deficiency is linked to defective NEMO ubiquitination
Authors: Temmerman Stephane T. , Ma Chi A. , Borges Louis , Kubin Marek , Liu Shuying , Derry Jonathan M. J. , Jain Ashish 
Published: June 2006

Abstract
Ectodermal dysplasia with immune deficiency (EDI) is caused by alterations in NEMO (nuclear factor [NF]–κB essential modulator). Most genetic mutations are located in exon 10 and affect the C-terminal zinc finger domain. However, the biochemical mechanism by which they cause immune dysfunction remains undetermined. In this report, we investigated the effect of a cysteine-to-arginine mutation (C417R) found in the NEMO zinc finger domain on dendritic cell (DC) function. Following CD40 stimulation of DCs prepared from 2 unrelated patients with the NEMO C417R mutation, we found NEMO ubiquitination was absent, and this was associated with preserved RelA but absent c-Rel activity. As a consequence, CD40 stimulated EDI DCs failed to synthesize the c-Rel–dependent cytokine interleukin-12, had impaired up-regulation of costimulatory molecules, and failed to support allogeneic lymphocyte proliferation in vitro. In contrast, EDI DCs stimulated with the TLR4 ligand lipopolysaccharide (LPS) showed normal downstream NF-κB activity, DC maturation, and NEMO ubiquitination. These findings show for the first time how mutations in the zinc finger domain of NEMO can lead to pathway specific defects in NEMO ubiquitination and thus immune deficiency.
BASH-novel PKC-Raf-1 pathway of pre-BCR signaling induces κ gene rearrangement
Authors: Yamamoto Mutsumi , Hayashi Katsuhiko , Nojima Takuya , Matsuzaki Yumi , Kawano Yohei , Karasuyama Hajime , Goitsuka Ryo , Kitamura Daisuke 
Published: June 2006

Abstract
The pre-B-cell receptor (pre-BCR) is thought to signal transcriptional activation of the immunoglobulin light (L) chain gene locus, proceeding to its V-J rearrangement. The pre-BCR signaling pathway for this process is largely unknown but may involve the adaptor protein BASH (BLNK/SLP-65). Here we report that the pre-B leukemia cell lines established from affected BASH-deficient mice rearrange κL-chain gene locus and down-regulate pre-BCR upon PMA treatment or BASH reconstitution. Analyses with specific inhibitors revealed that activation of novel PKC (nPKC) and MEK, but not Ras, is necessary for the rearrangement. Accordingly, retroviral transduction of active PKCη, PKCϵ, or Raf-1, but not Ras, induced the κ gene rearrangement and expression in the pre-B-cell line. Tamoxifen-mediated BASH reconstitution resulted in the translocation of PKCη to the plasma membrane and κ chain expression. These data make evident that the Ras-independent BASH-nPKC-Raf-1 pathway of pre-BCR signaling induces the L-chain gene rearrangement and expression.
Protein disorder prediction by condensed PSSM considering propensity for order or disorder
Authors: Su Chung-Tsai , Chen Chien-Yu , Ou Yu-Yen 
Published: June 2006

Abstract

Background
More and more disordered regions have been discovered in protein sequences, and many of them are found to be functionally significant. Previous studies reveal that disordered regions of a protein can be predicted by its primary structure, the amino acid sequence. One observation that has been widely accepted is that ordered regions usually have compositional bias toward hydrophobic amino acids, and disordered regions are toward charged amino acids. Recent studies further show that employing evolutionary information such as position specific scoring matrices (PSSMs) improves the prediction accuracy of protein disorder. As more and more machine learning techniques have been introduced to protein disorder detection, extracting more useful features with biological insights attracts more attention.

Results
This paper first studies the effect of a condensed position specific scoring matrix with respect to physicochemical properties (PSSMP) on the prediction accuracy, where the PSSMP is derived by merging several amino acid columns of a PSSM belonging to a certain property into a single column. Next, we decompose each conventional physicochemical property of amino acids into two disjoint groups which have a propensity for order and disorder respectively, and show by experiments that some of the new properties perform better than their parent properties in predicting protein disorder. In order to get an effective and compact feature set on this problem, we propose a hybrid feature selection method that inherits the efficiency of uni-variant analysis and the effectiveness of the stepwise feature selection that explores combinations of multiple features. The experimental results show that the selected feature set improves the performance of a classifier built with Radial Basis Function Networks (RBFN) in comparison with the feature set constructed with PSSMs or PSSMPs that adopt simply the conventional physicochemical properties.

Conclusion
Distinguishing disordered regions from ordered regions in protein sequences facilitates the exploration of protein structures and functions. Results based on independent testing data reveal that the proposed predicting model DisPSSMP performs the best among several of the existing packages doing similar tasks, without either under-predicting or over-predicting the disordered regions. Furthermore, the selected properties are demonstrated to be useful in finding discriminating patterns for order/disorder classification.
Differential prioritization between relevance and redundancy in correlation-based feature selection techniques for multiclass gene expression data
Authors: Ooi Chia Huey , Chetty Madhu , Teng Shyh Wei 
Published: June 2006

AbstractBackgroundDue to the large number of genes in a typical microarray dataset, feature selection looks set to play an important role in reducing noise and computational cost in gene expression-based tissue classification while improving accuracy at the same time. Surprisingly, this does not appear to be the case for all multiclass microarray datasets. The reason is that many feature selection techniques applied on microarray datasets are either rank-based and hence do not take into account correlations between genes, or are wrapper-based, which require high computational cost, and often yield difficult-to-reproduce results. In studies where correlations between genes are considered, attempts to establish the merit of the proposed techniques are hampered by evaluation procedures which are less than meticulous, resulting in overly optimistic estimates of accuracy.ResultsWe present two realistically evaluated correlation-based feature selection techniques which incorporate, in addition to the two existing criteria involved in forming a predictor set (relevance and redundancy), a third criterion called the degree of differential prioritization (DDP). DDP functions as a parameter to strike the balance between relevance and redundancy, providing our techniques with the novel ability to differentially prioritize the optimization of relevance against redundancy (and vice versa). This ability proves useful in producing optimal classification accuracy while using reasonably small predictor set sizes for nine well-known multiclass microarray datasets.ConclusionFor multiclass microarray datasets, especially the GCM and NCI60 datasets, DDP enables our filter-based techniques to produce accuracies better than those reported in previous studies which employed similarly realistic evaluation procedures.
Deciphering protein function during mitosis in PtK cells using RNAi
Authors: Stout Jane R , Rizk Rania S , Kline Susan L , Walczak Claire E 
Published: June 2006

Abstract

Background
Studying mitosis requires a system in which the dramatic movements of chromosomes and spindle microtubules can be visualized. PtK cells, due to their flat morphology and their small number of large chromosomes, allow microscopic visualizations to be readily performed.

Results
By performing RNAi in PtK cells, we can explore the function of many proteins important for spindle assembly and chromosome segregation. Although it is difficult to transfect DNA into PtK cells (efficiency ~ 10%), we have transfected a fluorescent siRNA at nearly 100% efficiency. Using a cDNA expression library, we then isolated a complete PtK MCAK (P-MCAK) cDNA. P-MCAK shares 81% identity to Human-MCAK (H-MCAK) protein and 66% identity to H-MCAK DNA. Knockdown of P-MCAK by RNAi caused defects in chromosome congression and defective spindle organization. Live imaging revealed that chromosomes had defects in congression and segregation, similar to what we found after microinjection of inhibitory anti-MCAK antibodies. Because it is laborious to isolate full-length clones, we explored using RT-PCR with degenerate primers to yield cDNA fragments from PtK cells from which to design siRNAs. We isolated a cDNA fragment of the mitotic kinesin Eg5 from PtK cells. This fragment is 93% identical to H-Eg5 protein and 87% identical to H-Eg5 DNA. A conserved 21 bp siRNA was used for RNAi in both HeLa and PtK cells in which Eg5 knockdown resulted in an increased mitotic index and cells with monopolar spindles. In addition, we used RT-PCR to isolate fragments of 5 additional genes, whose sequence identity ranged from 76 to 90% with human, mouse, or rat genes, suggesting that this strategy is feasible to apply to any gene of interest.

Conclusion
This approach will allow us to effectively probe mitotic defects from protein knockdowns by combining genomic information from other organisms with the tractable morphology of PtK cells.
Evidence for the association of the SLC22A4 and SLC22A5 genes with Type 1 Diabetes: a case control study
Authors: Santiago Jose Luis , Martínez Alfonso , de la Calle Hermenegildo , Fernández-Arquero Miguel , Figueredo M Ángeles , de la Concha Emilio G , Urcelay Elena 
Published: June 2006

Abstract

Background
Type 1 diabetes (T1D) is a chronic, autoimmune and multifactorial disease characterized by abnormal metabolism of carbohydrate and fat. Diminished carnitine plasma levels have been previously reported in T1D patients and carnitine increases the sensitivity of the cells to insulin. Polymorphisms in the carnitine transporters, encoded by the SLC22A4 and SLC22A5 genes, have been involved in susceptibility to two other autoimmune diseases, rheumatoid arthritis and Crohn's disease. For these reasons, we investigated for the first time the association with T1D of six single nucleotide polymorphisms (SNPs) mapping to these candidate genes: slc2F2, slc2F11, T306I, L503F, OCTN2-promoter and OCTN2-intron.

Methods
A case-control study was performed in the Spanish population with 295 T1D patients and 508 healthy control subjects. Maximum-likelihood haplotype frequencies were estimated by applying the Expectation-Maximization (EM) algorithm implemented by the Arlequin software.

Results
When independently analyzed, one of the tested polymorphisms in the SLC22A4 gene at 1672 showed significant association with T1D in our Spanish cohort. The overall comparison of the inferred haplotypes was significantly different between patients and controls (χ2 = 10.43; p = 0.034) with one of the haplotypes showing a protective effect for T1D (rs3792876/rs1050152/rs2631367/rs274559, CCGA: OR = 0.62 (0.41–0.93); p = 0.02).

Conclusion
The haplotype distribution in the carnitine transporter locus seems to be significantly different between T1D patients and controls; however, additional studies in independent populations would allow to confirm the role of these genes in T1D risk.
Ep-CAM expression in squamous cell carcinoma of the esophagus: a potential therapeutic target and prognostic marker
Authors: Stoecklein Nikolas H , Siegmund Annika , Scheunemann Peter , Luebke Andreas M , Erbersdobler Andreas , Verde Pablo E , Eisenberger Claus F , Peiper Matthias , Rehders Alexander , Esch Jan Schulte am , Knoefel Wolfram Trudo , Hosch Stefan B 
Published: June 2006

Abstract

Background
To evaluate the expression and test the clinical significance of the epithelial cellular adhesion molecule (Ep-CAM) in esophageal squamous cell carcinoma (SCC) to check the suitability of esophageal SCC patients for Ep-CAM directed targeted therapies.

Methods
The Ep-CAM expression was immunohistochemically investigated in 70 primary esophageal SCCs using the monoclonal antibody Ber-EP4. For the interpretation of the staining results, we used a standardized scoring system ranging from 0 to 3+. The survival analysis was calculated from 53 patients without distant metastasis, with R0 resection and at least 2 months of clinical follow-up.

Results
Ep-CAM neo-expression was observed in 79% of the tumors with three expression levels, 1+ (26%), 2+ (11%) and 3+ (41%). Heterogeneous expression was observed at all expression levels. Interestingly, tumors with 3+ Ep-CAM expression conferred a significantly decreased median relapse-free survival period (log rank, p = 0.0001) and median overall survival (log rank, p = 0.0003). Multivariate survival analysis disclosed Ep-CAM 3+ expression as independent prognostic factor.

Conclusion
Our results suggest Ep-CAM as an attractive molecule for targeted therapy in esophageal SCC. Considering the discontenting results of the current adjuvant concepts for esophageal SCC patients, Ep-CAM might provide a promising target for an adjuvant immunotherapeutic intervention.